Metastatic propagation of thyroid cancer; organ tropism and major modulators

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References

• 1. Vianna DM, Curioni OA, França LJDL et al. The histological rarity of thyroid cancer. Braz. J. Otorhinolaryngol. 78(4), 48–51 (2012).
  MedlineGoogle Scholar
• 2. Mendelsohn J, Howley PM, Israel MA, Gray JW, Thompson CB. The Molecular Basis of Cancer (Fourth Edition). Elsevier Inc., TX, USA, (2014).
  Google Scholar
• 3. Greco A, Miranda C, Borrello MG, Pierotti MA. Thyroid cancer. In: Cancer Genomics. Elsevier, MS, USA, 265–280 (2014).
  Google Scholar
• 4. Rajabi S, Hedayati M. Medullary thyroid cancer: clinical characteristics and new insights into therapeutic strategies targeting tyrosine kinases. Mol. Diag. Ther. 21(6), 607–620 (2017).
  Medline CASGoogle Scholar
• 5. Lin YH, Jang CS, Wu CS, Hsu L. Unusual presentation of anaplastic thyroid carcinoma with diffuse neck and thoracic nodules and hyperthyroidism. Dermatol. Sin. 35(2), 85–87 (2017).
  Google Scholar
• 6. O'Neill JP, Shaha AR. Anaplastic thyroid cancer. Oral. Oncol. 49(7), 702–706 (2013).
  MedlineGoogle Scholar
• 7. Jin S, Yang Y-T, Bao W. Signaling pathways in thyroid cancer. Vitam. Horm. 106, 501–515 (2017).
  MedlineGoogle Scholar
• 8. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19(11), 1423–1437 (2013).
  Medline CASGoogle Scholar
• 9. Salvatore V, Teti G, Focaroli S, Mazzotti MC, Mazzotti A, Falconi M. The tumor microenvironment promotes cancer progression and cell migration. Oncotarget 8(6), 9608 (2017).
  MedlineGoogle Scholar
• 10. Croucher PI, McDonald MM, Martin TJ. Bone metastasis: the importance of the neighbourhood. Nat. Rev. Cancer 16(6), 373–386 (2016).
  Medline CASGoogle Scholar
• 11. Martin TA, Ye L, Sanders AJ, Lane J, Jiang WG. Cancer invasion and metastasis: molecular and cellular perspective. In: Madame Curie Bioscience Database. Landes Bioscience, TX, USA (2013). www.ncbi.nlm.nih.gov/books/NBK164700/
  Google Scholar
• 12. Stivarou T, Patsavoudi E. Extracellular molecules involved in cancer cell invasion. Cancers 7(1), 238–265 (2015).
  Medline CASGoogle Scholar
• 13. Krakhmal N, Zavyalova M, Denisov E, Vtorushin S, Perelmuter V. Cancer invasion: patterns and mechanisms. Acta. Naturae 7(2), 17–28 (2015).
  Medline CASGoogle Scholar
• 14. Friedl P, Locker J, Sahai E, Segall JE. Classifying collective cancer cell invasion. Nat. Cell. Riol. 14(8), 777–783 (2012).
  MedlineGoogle Scholar
• 15. Yilmaz M, Christofori G. Mechanisms of motility in metastasizing cells. Mol. Cancer. Res. 8(5), 629–642 (2010).
  Medline CASGoogle Scholar
• 16. Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat. Rev. Mol. cell. Biol. 10(7), 445–457 (2009).
  Medline CASGoogle Scholar
• 17. Kitamura T, Kometani K, Hashida H et al. SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nat. Gen. 39(4), 467–476 (2007).
  Medline CASGoogle Scholar
• 18. Nieto MA. Epithelial plasticity: a common theme in embryonic and cancer cells. Science 342(6159), 1234850 (2013).
  MedlineGoogle Scholar
• 19. Chiang SP, Cabrera RM, Segall JE. Tumor cell intravasation. Am. J. Physiol. Cell. Physiol. 311(1), 1–14 (2016).
  Google Scholar
• 20. Dua R, Gui G, Isacke C. Endothelial adhesion molecules in breast cancer invasion into the vascular and lymphatic systems. Eur. J. Surg. Oncol. 31(8), 824–832 (2005).
  Medline CASGoogle Scholar
• 21. Shenoy AK, Lu J. Cancer cells remodel themselves and vasculature to overcome the endothelial barrier. Cancer Lett. 380(2), 534–544 (2016).
  Medline CASGoogle Scholar
• 22. Reymond N, d'Água BB, Ridley AJ. Crossing the endothelial barrier during metastasis. Nat. Rev. Cancer 13(12), 858–870 (2013).
  Medline CASGoogle Scholar
• 23. Entschladen F, Drell TL, Lang K, Joseph J, Zaenker KS. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters. Lancet Oncol. 5(4), 254–258 (2004).
  Medline CASGoogle Scholar
• 24. Azevedo AS, Follain G, Patthabhiraman S, Harlepp S, Goetz JG. Metastasis of circulating tumor cells: favorable soil or suitable biomechanics, or both? Cell Adh. Migr. 9(5), 345–356 (2015).
  Medline CASGoogle Scholar
• 25. Mishra AP, Salehi B, Sharifi-Rad M et al. Programmed cell death, from a cancer perspective: an overview. Mol. Diag. Ther. 22(3), 281–295 (2018).
  Medline CASGoogle Scholar
• 26. Hou J-M, Krebs MG, Lancashire L et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J. Clin. Oncol. 30(5), 525–532 (2012).
  MedlineGoogle Scholar
• 27. Mitchell MJ, King MR. Fluid shear stress sensitizes cancer cells to receptor-mediated apoptosis via trimeric death receptors. New J. Phys. 15(1), 015008 (2013).
  Medline CASGoogle Scholar
• 28. Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20(5), 576–590 (2011).
  Medline CASGoogle Scholar
• 29. Kunita A, Kashima TG, Morishita Y et al. The platelet aggregation-inducing factor aggrus/podoplanin promotes pulmonary metastasis. Am. J. Pathol. 170(4), 1337–1347 (2007).
  Medline CASGoogle Scholar
• 30. Takagi S, Sato S, Oh-Hara T et al. Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2. PLoS ONE 8(8), e73609 (2013).
  Medline CASGoogle Scholar
• 31. Strell C, Entschladen F. Extravasation of leukocytes in comparison to tumor cells. Cell Com. Sig. 6(1), 10 (2008).
  MedlineGoogle Scholar
• 32. Bendas G, Borsig L. Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int. J. Cell. Biol. 2012, doi: 10.1155/2012/676731 (2012) (Epub ahead of print).
  MedlineGoogle Scholar
• 33. Shibue T, Weinberg RA. Metastatic colonization: settlement, adaptation and propagation of tumor cells in a foreign tissue environment. Semin. Cancer Biol. 21(2), 99–106 (2011).
  Medline CASGoogle Scholar
• 34. Chambers A, Groom A, MacDonald I. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2(8), 563–572 (2002).
  Medline CASGoogle Scholar
• 35. Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat. Rev. Cancer 9(4), 274–284 (2009).
  Medline CASGoogle Scholar
• 36. Irmisch A, Huelsken J. Metastasis: new insights into organ-specific extravasation and metastatic niches. Exp. Cell Res. 319(11), 1604–1610 (2013). • It interestingly explains alternative hypoteses for seed and soil theory.
  Medline CASGoogle Scholar
• 37. Lu X, Kang Y. Organotropism of breast cancer metastasis. J. Mammary. Gland. Biol. Neoplasia 12(2–3), 153 (2007).
  MedlineGoogle Scholar
• 38. Chen W, Hoffmann AD, Liu H, Liu X. Organotropism: new insights into molecular mechanisms of breast cancer metastasis. NPJ Precis. Oncol. 2(1), 4 (2018).
  MedlineGoogle Scholar
• 39. Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell 30(5), 668–681 (2016). • Because of the description of premetastatic niche features to promote tumor cell colonization and metastasis.
  Medline CASGoogle Scholar
• 40. Ursini-Siegel J, Siegel PM. The influence of the pre-metastatic niche on breast cancer metastasis. Cancer Lett. 380(1), 281–288 (2016).
  Medline CASGoogle Scholar
• 41. Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat. Rev. Cancer 9(4), 285 (2009).
  Medline CASGoogle Scholar
• 42. Obenauf AC, Massagué J. Surviving at a distance: organ-specific metastasis. Trends Cancer 1(1), 76–91 (2015).
  MedlineGoogle Scholar
• 43. Urosevic J, Garcia-Albéniz X, Planet E et al. Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH. Nat. Cell. Biol. 16(7), 685 (2014).
  Medline CASGoogle Scholar
• 44. Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat. Rev. Cancer 9(4), 274 (2009).
  Medline CASGoogle Scholar
• 45. Budczies J, Von Winterfeld M, Klauschen F et al. The landscape of metastatic progression patterns across major human cancers. Oncotarget 6(1), 570 (2015).
  MedlineGoogle Scholar
• 46. Nixon IJ, Whitcher MM, Palmer FL et al. The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland. Thyroid 22(9), 884–889 (2012).
  MedlineGoogle Scholar
• 47. Hirsch D, Levy S, Tsvetov G et al. Long-term outcomes and prognostic factors in patients with differentiated thyroid cancer and distant metastases. Endocr. Pract. 23(10), 1193–1200 (2017).
  MedlineGoogle Scholar
• 48. Sohn SY, Kim HI, Kim YN, Kim TH, Kim SW, Chung JH. Prognostic indicators of outcomes in patients with lung metastases from differentiated thyroid carcinoma during long-term follow-up. Clin. Endocrinol. 88(2), 318–326 (2018).
  Medline CASGoogle Scholar
• 49. Sampson E, Brierley JD, Le LW, Rotstein L, Tsang RW. Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis. Cancer 110(7), 1451–1456 (2007). • Because it is very informative due to describing thyroid cancer organotropism.
  MedlineGoogle Scholar
• 50. Lin JD, Liou MJ, Chao TC, Weng HF, Ho YS. Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases. Endocr. Rel. Cancer. 6(1), 109–115 (1999).
  Medline CASGoogle Scholar
• 51. Mizrachi A, Shaha AR. Lymph node dissection for differentiated thyroid cancer. Mol. Imaging Radionucl. Ther. 26(1), 10 (2017).
  MedlineGoogle Scholar
• 52. Lai X-J, Zhang B, Jiang Y-X et al. High Risk of lateral nodal metastasis in lateral solitary solid papillary thyroid cancer. Ultrasound Med. Biol. 42(1), 75–81 (2016).
  MedlineGoogle Scholar
• 53. So YK, Kim M-J, Kim S, Son Y-I. Lateral lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis for prevalence, risk factors, and location. Int. J. Surg. 50, 94–103 (2018).
  MedlineGoogle Scholar
• 54. Batawil N. Papillary thyroid cancer with bilateral adrenal metastases. Thyroid 23(12), 1651–1654 (2013).
  MedlineGoogle Scholar
• 55. Wagenaar N, Oosterhuis JWA, Rozendaal L, Comans E, Simsek S. Adrenal metastasis from a primary papillary thyroid carcinoma. Intern. Med. 47(24), 2165–2168 (2008).
  MedlineGoogle Scholar
• 56. Ranade R, Thapa P, Basu S. Adrenal metastasis from differentiated thyroid carcinoma documented on post-therapy 131I scan: a case based discussion. World J. Radiol. 6(3), 56 (2014).
  MedlineGoogle Scholar
• 57. Malhotra G, Upadhye TS, Sridhar E et al. Unusual case of adrenal and renal metastases from papillary carcinoma of thyroid. Clin. Nucl. Med. 35(9), 731–736 (2010).
  MedlineGoogle Scholar
• 58. Altinay S, Tas B, Ozen A, Sut PA. Anaplastic thyroid carcinoma with diffuse thoracic skin metastasis: a case report. Oncol. Lett. 7(6), 1767–1770 (2014).
  MedlineGoogle Scholar
• 59. Solomon JP, Wen F, Jih LJ. Anaplastic transformation of papillary thyroid cancer in the retroperitoneum. Case Rep. Pathol. 2015, 241308 (2015).
  MedlineGoogle Scholar
• 60. Ambelil M, Sultana S, Roy S, Gonzalez MM. Anaplastic transformation in mandibular metastases of follicular variant of papillary thyroid carcinoma: a case report and review of the literature. Ann. Clin. Lab. Sci. 46(5), 552–556 (2016).
  MedlineGoogle Scholar
• 61. Kaushal S, Sharma MC, Mathur SR, Rastogi S, Bal CS, Chumber S. Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma. Indian J. Pathol. Microbiol. 54(4), 796–799 (2011).
  MedlineGoogle Scholar
• 62. Lee W, Kim D. Anaplastic transformation of follicular thyroid cancer in the lung, liver, bone, and adrenal gland. Int. J. Thyroidol. 10(2), 127–132 (2017).
  Google Scholar
• 63. Besic N, Gazic B. Sites of metastases of anaplastic thyroid carcinoma: autopsy findings in 45 cases from a single institution. Thyroid 23(6), 709–713 (2013).
  MedlineGoogle Scholar
• 64. Giuffrida D, Gharib H. Cardiac metastasis from primary anaplastic thyroid carcinoma: report of three cases and a review of the literature. Endocr. Relat. Cancer 8(1), 71–73 (2001).
  Medline CASGoogle Scholar
• 65. Sastry R, Williams EA, Koffie R, Fehnel K, Wirth L, Nahed B. Metastatic medullary thyroid cancer to the brain: a case report and review of the literature. Int. J. Endocr. Oncol. 5(3), IJE11 (2018).
  CASGoogle Scholar
• 66. Mandanas S, Margaritidou E, Christoforidou V et al. Breast metastasis from medullary thyroid carcinoma in a male patient: case report and review of the literature. Rare Tumors 7(2), 5765 (2015).
  MedlineGoogle Scholar
• 67. Tanwar P, Gandhi JS, Sharma A, Gupta M, Choudhary PS. Unusual metastasis of medullary thyroid carcinoma to the breast: a cytological and histopathological correlation. J. Cytol. 35(2), 117–120 (2018).
  MedlineGoogle Scholar
• 68. Sato S, Okumura Y, Tamizu A et al. Detection of hepatic metastasis from medullary thyroid cancer with Tc-99m-MIBI scintigraphy in a patient with Sipple's syndrome. Ann. Nucl. Med. 15(5), 443–446 (2001).
  Medline CASGoogle Scholar
• 69. Niafar M, Dabiri S, Bozorgi F, Niafar F, Gholami N. Metastatic medullary thyroid carcinoma: a case report. J. Res. Med. Sci. 16(4), 568–573 (2011).
  MedlineGoogle Scholar
• 70. Manzella L, Stella S, Pennisi MS et al. New insights in thyroid cancer and p53 family proteins. Int. J. Mol. Sci. 18(6), 1325 (2017).
  Google Scholar
• 71. Song JY, Sun SR, Dong F, Huang T, Wu B, Zhou J. Predictive value of BRAF(V600E) mutation for lymph node metastasis in papillary thyroid cancer: a meta-analysis. Curr. Med. Sci. 38(5), 785–797 (2018).
  Medline CASGoogle Scholar
• 72. Trybek T, Walczyk A, Gasior-Perczak D et al. Impact of BRAF V600E and TERT promoter mutations on response to therapy in papillary thyroid cancer. Endocrinology 160(10), 2328–2338 (2019).
  Medline CASGoogle Scholar
• 73. Huang M, Yan C, Xiao J, Wang T, Ling R. Relevance and clinicopathologic relationship of BRAF V600E, TERT and NRAS mutations for papillary thyroid carcinoma patients in Northwest China. Diagn. Pathol. 14(1), 74 (2019).
  MedlineGoogle Scholar
• 74. Xing M, Liu R, Liu X et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J. Clin. Oncol. 32(25), 2718–2726 (2014).
  Medline CASGoogle Scholar
• 75. Shi X, Liu R, Qu S et al. Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer. J. Clin. Endocrinol. Metab. 100(4), 632–637 (2015).
  Google Scholar
• 76. Li Y, Chen D, Hao FY, Zhang KJ. Targeting TGF-beta1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo. Eur. Rev. Med. Pharmacol. Sci. 20(12), 2581–2587 (2016).
  Medline CASGoogle Scholar
• 77. Ricarte-Filho JC, Ryder M, Chitale DA et al. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res. 69(11), 4885–4893 (2009).
  Medline CASGoogle Scholar
• 78. Sadowski SM, Boufraqech M, Zhang L et al. Torin2 targets dysregulated pathways in anaplastic thyroid cancer and inhibits tumor growth and metastasis. Oncotarget 6(20), 18038–18049 (2015).
  MedlineGoogle Scholar
• 79. Zaballos MA, Santisteban P. Key signaling pathways in thyroid cancer. J. Endocrinol. 235(2), R43–R61 (2017).
  Medline CASGoogle Scholar
• 80. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell 147(2), 275–292 (2011).
  Medline CASGoogle Scholar
• 81. Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 24(37), 5764–5774 (2005).
  Medline CASGoogle Scholar
• 82. Lebrun JJ. The dual role of TGFβ in human cancer: from tumor suppression to cancer metastasis. Mol. Biol. 2012, 381428 (2012).
  Google Scholar
• 83. Ivanova K, Manolova I, Ignatova MM, Gulubova M. Immunohistochemical expression of TGF-B1, SMAD4, SMAD7, TGFβRII and CD68-positive TAM densities in papillary thyroid cancer. Open Access Maced. J. Med. Sci. 6(3), 435–441 (2018).
  MedlineGoogle Scholar
• 84. D'inzeo S, Nicolussi A, Donini CF et al. A novel human Smad4 mutation is involved in papillary thyroid carcinoma progression. Endocr. Relat. Cancer 19(1), 39–55 (2012).
  MedlineGoogle Scholar
• 85. Cerutti JM, Ebina KN, Matsuo SE, Martins L, Maciel RM, Kimura ET. Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines. J. Endocrinol. Invest. 26(6), 516–521 (2003).
  Medline CASGoogle Scholar
• 86. Ulisse S, Delcros JG, Baldini E et al. Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Int. J. Cancer 119(2), 275–282 (2006).
  Medline CASGoogle Scholar
• 87. Tang A, Gao K, Chu L, Zhang R, Yang J, Zheng J. Aurora kinases: novel therapy targets in cancers. Oncotarget 8(14), 23937–23954 (2017).
  MedlineGoogle Scholar
• 88. Cazzaniga M, Bonanni B. Relationship between metabolic reprogramming and mitochondrial activity in cancer cells. understanding the anticancer effect of metformin and its clinical implications. Anticancer Res. 35(11), 5789–5796 (2015).
  Medline CASGoogle Scholar
• 89. Liu CL, Yang PS, Wang TY, Huang SY, Kuo YH, Cheng SP. PGC1alpha downregulation and glycolytic phenotype in thyroid cancer. J. Cancer 10(16), 3819–3829 (2019).
  Medline CASGoogle Scholar
• 90. Sasaki H, Suzuki A, Shitara M et al. Angiopoietin-like protein ANGPTL2 gene expression is correlated with lymph node metastasis in lung cancer. Oncol. Lett. 4(6), 1325–1328 (2012).
  Medline CASGoogle Scholar
• 91. Yoshinaga T, Shigemitsu T, Nishimata H et al. Angiopoietin-like protein 2 as a potential biomarker for colorectal cancer. Mol. Clin. Oncol. 3(5), 1080–1084 (2015).
  Medline CASGoogle Scholar
• 92. Sheng WZ, Chen YS, Tu CT, He J, Zhang B, Gao WD. ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior. World J. Gastroenterol. 22(47), 10364–10370 (2016).
  Medline CASGoogle Scholar
• 93. Sato R, Yamasaki M, Hirai K et al. Angiopoietin-like protein 2 induces androgen-independent and malignant behavior in human prostate cancer cells. Oncol. Rep. 33(1), 58–66 (2015).
  Medline CASGoogle Scholar
• 94. Yang L, Sun R, Wang Y et al. Expression of ANGPTL2 and its impact on papillary thyroid cancer. Cancer Cell. Int. 19, 204 (2019).
  MedlineGoogle Scholar
• 95. Kang YE, Kim JT, Lim MA et al. Association between circulating fibroblast growth factor 21 and aggressiveness in thyroid cancer. Cancers (Basel) 11(8), 1154 (2019).
  CASGoogle Scholar
• 96. Mack GS, Marshall A. Lost in migration. Nat. Biotechnol. 28(3), 214–229 (2010).
  Medline CASGoogle Scholar
• 97. Singh D, Srivastava SK, Chaudhuri TK, Upadhyay G. Multifaceted role of matrix metalloproteinases (MMPs). Front. Mol. Biosci. 2, 19 (2015).
  MedlineGoogle Scholar
• 98. Tian X, Cong M, Zhou W, Zhu J, Liu Q. Relationship between protein expression of VEGF-C, MMP-2 and lymph node metastasis in papillary thyroid cancer. J. Int. Med. Res. 36(4), 699–703 (2008).
  Medline CASGoogle Scholar
• 99. Luo D, Chen H, Li X et al. Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma. Int. J. Oncol. 51(4), 1209–1218 (2017).
  Medline CASGoogle Scholar
• 100. Ito Y, Yoshida H, Kakudo K, Nakamura Y, Kuma K, Miyauchi A. Inverse relationships between the expression of MMP-7 and MMP-11 and predictors of poor prognosis of papillary thyroid carcinoma. Pathology 38(5), 421–425 (2006).
  Medline CASGoogle Scholar
• 101. Kim S, Kang HY, Nam EH et al. TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways. Carcinogenesis 31(4), 597–606 (2010).
  Medline CASGoogle Scholar
• 102. Guan H, Liang W, Liu J et al. Transmembrane protease serine 4 promotes thyroid cancer proliferation via CREB phosphorylation. Thyroid 25(1), 85–94 (2015).
  Medline CASGoogle Scholar
• 103. Mahmood N, Mihalcioiu C, Rabbani SA. Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front. Oncol. 8, 24 (2018).
  MedlineGoogle Scholar
• 104. Ulisse S, Baldini E, Sorrenti S et al. High expression of the urokinase plasminogen activator and its cognate receptor associates with advanced stages and reduced disease-free interval in papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 96(2), 504–508 (2011).
  Medline CASGoogle Scholar
• 105. Nowicki TS, Kummer NT, Iacob C et al. Inhibition of uPAR and uPA reduces invasion in papillary thyroid carcinoma cells. Laryngoscope 120(7), 1383–1390 (2010).
  Medline CASGoogle Scholar
• 106. Nowicki TS, Zhao H, Darzynkiewicz Z et al. Downregulation of uPAR inhibits migration, invasion, proliferation, FAK/PI3K/Akt signaling and induces senescence in papillary thyroid carcinoma cells. Cell Cycle 10(1), 100–107 (2011).
  Medline CASGoogle Scholar
• 107. Liu L, Jung SN, Oh C et al. LAMB3 is associated with disease progression and cisplatin cytotoxic sensitivity in head and neck squamous cell carcinoma. Eur. J. Surg. Oncol. 45(3), 359–365 (2019).
  MedlineGoogle Scholar
• 108. Wang Y, Jin Y, Bhandari A et al. Upregulated LAMB3 increases proliferation and metastasis in thyroid cancer. Onco Targets. Ther. 11, 37–46 (2018).
  MedlineGoogle Scholar
• 109. Huang LL, Wang Z, Cao CJ et al. AEG-1 associates with metastasis in papillary thyroid cancer through upregulation of MMP2/9. Int. J. Oncol. 51(3), 812–822 (2017).
  Medline CASGoogle Scholar
• 110. Zhu QC, Gao RY, Wu W, Qin HL. Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer. Asian Pac. J. Cancer. Prev. 14(5), 2689–2698 (2013).
  MedlineGoogle Scholar
• 111. Sanchez-Tillo E, Lazaro A, Torrent R et al. ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene 29(24), 3490–3500 (2010).
  Medline CASGoogle Scholar
• 112. Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr. Opin. Cell Biol. 17(5), 548–558 (2005).
  Medline CASGoogle Scholar
• 113. Mrozik KM, Blaschuk OW, Cheong CM, Zannettino ACW, Vandyke K. N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer 18(1), 939 (2018).
  Medline CASGoogle Scholar
• 114. Shakib H, Rajabi S, Dehghan MH, Mashayekhi FJ, Safari-Alighiarloo N, Hedayati M. Epithelial-to-mesenchymal transition in thyroid cancer: a comprehensive review. Endocrine 66(3), 435–455 (2019).
  Medline CASGoogle Scholar
• 115. Van Staalduinen J, Baker D, Ten Dijke P, Van Dam H. Epithelial-mesenchymal-transition-inducing transcription factors: new targets for tackling chemoresistance in cancer? Oncogene 37(48), 6195–6211 (2018).
  Medline CASGoogle Scholar
• 116. Wu J, Zhang Y, Cheng R et al. Expression of epithelial-mesenchymal transition regulators TWIST, SLUG and SNAIL in follicular thyroid tumours may relate to widely invasive, poorly differentiated and distant metastasis. Histopathology 74(5), 780–791 (2019).
  MedlineGoogle Scholar
• 117. Meng X, Kong DH, Li N et al. Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation. Cell Death Dis. 5, e1092 (2014).
  Medline CASGoogle Scholar
• 118. Huang J, Guo L. Knockdown of SOX9 inhibits the proliferation, invasion, and EMT in thyroid cancer cells. Oncol. Res. 25(2), 167–176 (2017).
  MedlineGoogle Scholar
• 119. Niu DF, Kondo T, Nakazawa T et al. Transcription factor Runx2 is a regulator of epithelial-mesenchymal transition and invasion in thyroid carcinomas. Lab. Invest. 92(8), 1181–1190 (2012).
  Medline CASGoogle Scholar
• 120. Yin H, Meng T, Zhou L et al. FOXD3 regulates anaplastic thyroid cancer progression. Oncotarget 8(20), 33644–33651 (2017).
  MedlineGoogle Scholar
• 121. Wang N, Li Y, Wei J et al. TBX1 Functions as a tumor suppressor in thyroid cancer through inhibiting the activities of the PI3K/AKT and MAPK/ERK pathways. Thyroid 29(3), 378–394 (2019).
  Medline CASGoogle Scholar
• 122. Hao RT, Zheng C, Wu CY et al. NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT. Cancer Manag. Res. 11, 2565–2578 (2019).
  Medline CASGoogle Scholar
• 123. Bhandari A, Guan Y, Xia E, Huang Q, Chen Y. VASN promotes YAP/TAZ and EMT pathway in thyroid carcinogenesis in vitro. Am. J. Transl. Res. 11(6), 3589–3599 (2019).
  Medline CASGoogle Scholar
• 124. Wang X, Xu X, Peng C et al. BRAF(V600E)-induced KRT19 expression in thyroid cancer promotes lymph node metastasis via EMT. Oncol. Lett. 18(1), 927–935 (2019).
  Medline CASGoogle Scholar
• 125. Liu T, Men Q, Su X et al. Downregulated expression of TSHR is associated with distant metastasis in thyroid cancer. Oncol. Lett. 14(6), 7506–7512 (2017). • Because it points out to role of TSH receptor in epithelial–mesenchymal transition process in differentiated thyroid cancer.
  MedlineGoogle Scholar
• 126. Heery R, Finn SP, Cuffe S, Gray SG. Long non-coding RNAs: key regulators of epithelial-mesenchymal transition, tumour drug resistance and cancer stem cells. Cancers (Basel) 9(4), 38 (2017).
  MedlineGoogle Scholar
• 127. Gugnoni M, Ciarrocchi A. Long noncoding RNA and epithelial mesenchymal transition in cancer. Int. J. Mol. Sci. 20(8), 1924 (2019).
  CASGoogle Scholar
• 128. Lei H, Gao Y, Xu X. LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145. Acta Biochim. Biophys. Sin. 49(7), 588–597 (2017).
  CASGoogle Scholar
• 129. Wang Y, Gu J, Lin X, Yan W, Yang W, Wu G. lncRNA BANCR promotes EMT in PTC via the Raf/MEK/ERK signaling pathway. Oncol. Lett. 15(4), 5865–5870 (2018).
  MedlineGoogle Scholar
• 130. Xia E, Bhandari A, Shen Y, Zhou X, Wang O. lncRNA LINC00673 induces proliferation, metastasis and epithelial-mesenchymal transition in thyroid carcinoma via Kruppel-like factor 2. Int. J. Oncol. 53(5), 1927–1938 (2018).
  Medline CASGoogle Scholar
• 131. Zhang R, Hardin H, Huang W, Buehler D, Lloyd RV. Long Non-coding RNA Linc-ROR Is upregulated in papillary thyroid carcinoma. Endocr. Pathol. 29(1), 1–8 (2018).
  MedlineGoogle Scholar
• 132. Di W, Li Q, Shen W, Guo H, Zhao S. The long non-coding RNA HOTAIR promotes thyroid cancer cell growth, invasion and migration through the miR-1-CCND2 axis. Am. J. Cancer. Res. 7(6), 1298–1309 (2017).
  Medline CASGoogle Scholar
• 133. Zhou T, Zhong M, Zhang S et al. LncRNA CASC2 expression is down-regulated in papillary thyroid cancer and promotes cell invasion by affecting EMT pathway. Cancer Biomark. 23(2), 185–191 (2018).
  Medline CASGoogle Scholar
• 134. Garcia-Sancha N, Corchado-Cobos R, Perez-Losada J, Canueto J. MicroRNA dysregulation in cutaneous squamous cell carcinoma. Int. J. Mol. Sci. 20(9), 2181 (2019).
  CASGoogle Scholar
• 135. Yu C, Zhang L, Luo D et al. MicroRNA-146b-3p promotes cell metastasis by directly targeting NF2 in human papillary thyroid cancer. Thyroid 28(12), 1627–1641 (2018).
  Medline CASGoogle Scholar
• 136. Liu Y, Li J, Li M, Li F, Shao Y, Wu L. microRNA-510-5p promotes thyroid cancer cell proliferation, migration, and invasion through suppressing SNHG15. J. Cell. Biochem. 120(7), 11738–11744 (2019).
  CASGoogle Scholar
• 137. Wang S, Chen X, Zhang Z, Wu Z. MicroRNA-1225-5p inhibits the development and progression of thyroid cancer via targeting sirtuin 3. Pharmazie 74(7), 423–427 (2019).
  Medline CASGoogle Scholar
• 138. Zhou A, Chen G, Cheng X et al. Inhibitory effects of miR26b5p on thyroid cancer. Mol. Med. Rep. 20(2), 1196–1202 (2019).
  Medline CASGoogle Scholar
• 139. Wang F, Li Z, Sun B. miR-544 inhibits the migration and invasion of anaplastic thyroid cancer by targeting Yin Yang-1. Oncol. Lett. 17(3), 2983–2992 (2019).
  Medline CASGoogle Scholar
• 140. Wang M, Yu F, Wu W et al. Circular RNAs: a novel type of non-coding RNA and their potential implications in antiviral immunity. Int. J. Biol. Sci. 13(12), 1497–1506 (2017).
  Medline CASGoogle Scholar
• 141. Yao Y, Chen X, Yang H et al. Hsa_circ_0058124 promotes papillary thyroid cancer tumorigenesis and invasiveness through the NOTCH3/GATAD2A axis. J. Exp. Clin. Cancer. Res. 38(1), 318 (2019).
  Medline CASGoogle Scholar
• 142. Yang Y, Ding L, Li Y, Xuan C. Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179/ABCA9 and miR-1205/MTA1 signaling pathways. J. Cell. Physiol. 235(2), 1321–1329 (2020).
  Medline CASGoogle Scholar
• 143. Martin AR, Ronco C, Demange L, Benhida R. Hypoxia inducible factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories. Medchemcomm 8(1), 21–52 (2017).
  Medline CASGoogle Scholar
• 144. Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J. Natl Cancer Inst. 93(4), 266–276 (2001).
  Medline CASGoogle Scholar
• 145. Choudhry H, Harris AL. Advances in hypoxia-inducible factor biology. Cell. Metab. 27(2), 281–298 (2018).
  Medline CASGoogle Scholar
• 146. Tan C, Zhang L, Cheng X et al. Curcumin inhibits hypoxia-induced migration in K1 papillary thyroid cancer cells. Exp. Biol. Med. 240(7), 925–935 (2015).
  CASGoogle Scholar
• 147. Koperek O, Akin E, Asari R, Niederle B, Neuhold N. Expression of hypoxia-inducible factor 1 alpha in papillary thyroid carcinoma is associated with desmoplastic stromal reaction and lymph node metastasis. Virchows Arch. 463(6), 795–802 (2013).
  Medline CASGoogle Scholar
• 148. Ding ZY, Huang YJ, Tang JD, Li G, Jiang PQ, Wu HT. Silencing of hypoxia-inducible factor-1alpha promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2. Exp. Ther. Med. 12(6), 3735–3741 (2016).
  Medline CASGoogle Scholar
• 149. Rajabi S, Dehghan MH, Dastmalchi R, Jalali Mashayekhi F, Salami S, Hedayati M. The roles and role-players in thyroid cancer angiogenesis. Endocr. J. 66(4), 277–293 (2019).
  Medline CASGoogle Scholar
• 150. Shi GH, Zhou L. Emodin suppresses angiogenesis and metastasis in anaplastic thyroid cancer by affecting TRAF6-mediated pathways in vivo and in vitro. Mol. Med. Rep. 18(6), 5191–5197 (2018).
  Medline CASGoogle Scholar
• 151. Xu DH, Zhu Z, Wakefield MR, Xiao H, Bai Q, Fang Y. The role of IL-11 in immunity and cancer. Cancer Lett. 373(2), 156–163 (2016).
  Medline CASGoogle Scholar
• 152. Zhong Z, Hu Z, Jiang Y et al. Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3beta signaling pathway activation. Oncotarget 7(37), 59652–59663 (2016).
  MedlineGoogle Scholar
• 153. Chong ST, Tan KM, Kok CYL et al. IL13RA2 Is Differentially regulated in papillary thyroid carcinoma vs follicular thyroid carcinoma. J. Clin. Endocrinol. Metab. 104(11), 5573–5584 (2019).
  MedlineGoogle Scholar
• 154. Yang YF, Lee YC, Lo S et al. A positive feedback loop of IL-17B-IL-17RB activates ERK/beta-catenin to promote lung cancer metastasis. Cancer Lett. 422, 44–55 (2018).
  Medline CASGoogle Scholar
• 155. Ren L, Xu Y, Liu C, Wang S, Qin G. IL-17RB enhances thyroid cancer cell invasion and metastasis via ERK1/2 pathway-mediated MMP-9 expression. Mol. Immunol. 90, 126–135 (2017).
  Medline CASGoogle Scholar
• 156. Rotondi M, Coperchini F, Latrofa F, Chiovato L. Role of chemokines in thyroid cancer microenvironment: is CXCL8 the main player? Front. Endocrinol. 9, 314 (2018).
  MedlineGoogle Scholar
• 157. Mollica Poeta V, Massara M, Capucetti A, Bonecchi R. Chemokines and chemokine receptors: new targets for cancer immunotherapy. Front. Immunol. 10, 379 (2019).
  MedlineGoogle Scholar
• 158. Borrello MG, Alberti L, Fischer A et al. Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc. Natl Acad. Sci.USA 102(41), 14825–14830 (2005).
  Medline CASGoogle Scholar
• 159. Basolo F, Giannini R, Toniolo A et al. Establishment of a non-tumorigenic papillary thyroid cell line (FB-2) carrying the RET/PTC1 rearrangement. Int. J. Cancer 97(5), 608–614 (2002).
  Medline CASGoogle Scholar
• 160. Tang C, Yang L, Wang N et al. High expression of GPER1, EGFR and CXCR1 is associated with lymph node metastasis in papillary thyroid carcinoma. Int. J. Clin. Exp. Pathol. 7(6), 3213–3223 (2014).
  Medline CASGoogle Scholar
• 161. Pinchot SN, Sippel RS, Chen H. Multi-targeted approach in the treatment of thyroid cancer. Ther. Clin. Risk. Manag. 4(5), 935–947 (2008).
  Medline CASGoogle Scholar
• 162. Grewal RK, Ho A, Schoder H. Novel approaches to thyroid cancer treatment and response assessment. Semin. Nucl. Med. 46(2), 109–118 (2016).
  MedlineGoogle Scholar
• 163. Saini S, Tulla K, Maker AV, Burman KD, Prabhakar BS. Therapeutic advances in anaplastic thyroid cancer: a current perspective. Mol. Cancer 17(1), 154 (2018).
  Medline CASGoogle Scholar
• 164. Capozzi M, De Divitiis C, Ottaiano A et al. Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment. Cancer Manag. Res. 11, 3847–3860 (2019).
  Medline CASGoogle Scholar
• 165. Pitoia F, Jerkovich F. Selective use of sorafenib in the treatment of thyroid cancer. Drug Des. Devel. Ther. 10, 1119–1131 (2016).
  Medline CASGoogle Scholar
• 166. Dadu R, Devine C, Hernandez M et al. Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib. J. Clin. Endocrinol. Metab. 99(6), 2086–2094 (2014).
  Medline CASGoogle Scholar
• 167. Hu MI, Elisei R, Dedecjus M et al. Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer. Endocr. Relat. Cancer 26(2), 241–250 (2019).
  Medline CASGoogle Scholar
• 168. Leboulleux S, Bastholt L, Krause T et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, Phase II trial. Lancet Oncol. 13(9), 897–905 (2012).
  Medline CASGoogle Scholar
• 169. Ferrari SM, Bocci G, Di Desidero T et al. Vandetanib has antineoplastic activity in anaplastic thyroid cancer, in vitro and in vivo. Oncol. Rep. 39(5), 2306–2314 (2018).
  Medline CASGoogle Scholar
• 170. Grullich C. Cabozantinib: multi-kinase inhibitor of MET, AXL, RET, and VEGFR2. Recent Results Cancer Res. 211, 67–75 (2018).
  MedlineGoogle Scholar
• 171. Carvalho DP, Ferreira AC. The importance of sodium/iodide symporter (NIS) for thyroid cancer management. Arq. Bras. Endocrinol. Metabol. 51(5), 672–682 (2007).
  MedlineGoogle Scholar
• 172. Coelho SM, Vaisman M, Carvalho DP. Tumour re-differentiation effect of retinoic acid: a novel therapeutic approach for advanced thyroid cancer. Curr. Pharm. Des. 11(19), 2525–2531 (2005).
  Medline CASGoogle Scholar
• 173. Yu XM, Jaskula-Sztul R, Ahmed K, Harrison AD, Kunnimalaiyaan M, Chen H. Resveratrol induces differentiation markers expression in anaplastic thyroid carcinoma via activation of Notch1 signaling and suppresses cell growth. Mol. Cancer Ther. 12(7), 1276–1287 (2013).
  Medline CASGoogle Scholar
• 174. Fernandez LP, Lopez-Marquez A, Santisteban P. Thyroid transcription factors in development, differentiation and disease. Nat. Rev. Endocrinol. 11(1), 29–42 (2015).
  Medline CASGoogle Scholar
• 175. Yu XM, Phan T, Patel PN, Jaskula-Sztul R, Chen H. Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo. Cancer 119(4), 774–781 (2013).
  Medline CASGoogle Scholar
• 176. Hardin H, Yu XM, Harrison AD et al. Generation of novel thyroid cancer stem-like cell clones: effects of resveratrol and valproic acid. Am. J. Pathol. 186(6), 1662–1673 (2016).
  Medline CASGoogle Scholar
• 177. Peng W, Wang K, Zheng R, Derwahl M. 1,25 dihydroxyvitamin D3 inhibits the proliferation of thyroid cancer stem-like cells via cell cycle arrest. Endocr. Res. 41(2), 71–80 (2016).
  Medline CASGoogle Scholar
• 178. Patel PN, Yu XM, Jaskula-Sztul R, Chen H. Hesperetin activates the Notch1 signaling cascade, causes apoptosis, and induces cellular differentiation in anaplastic thyroid cancer. Ann. Surg. Oncol. 21(Suppl. 4), S497–S504 (2014).
  MedlineGoogle Scholar
• 179. Haghpanah V, Malehmir M, Larijani B et al. The beneficial effects of valproic acid in thyroid cancer are mediated through promoting redifferentiation and reducing stemness level: an in vitro study. J. Thyroid. Res. 2014, 218763 (2014).
  MedlineGoogle Scholar
• 180. Antonelli A, Bocci G, La Motta C et al. Novel pyrazolopyrimidine derivatives as tyrosine kinase inhibitors with antitumoral activity in vitro and in vivo in papillary dedifferentiated thyroid cancer. J. Clin. Endocrinol. Metab. 96(2), E288–E296 (2011).
  Medline CASGoogle Scholar
• 181. Fallahi P, Ferrari SM, La Motta C et al. CLM29 and CLM24, pyrazolopyrimidine derivatives, have antitumoral activity in vitro in anaplastic thyroid cancer, with or without BRAF mutation. Endocrine 53(1), 136–144 (2016).
  Medline CASGoogle Scholar
• 182. White PT, Subramanian C, Zhu Q et al. Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion. Surgery 159(1), 142–151 (2016).
  MedlineGoogle Scholar
• 183. Lin SF, Lin JD, Hsueh C et al. Efficacy of an HSP90 inhibitor, ganetespib, in preclinical thyroid cancer models. Oncotarget 8(25), 41294–41304 (2017).
  MedlineGoogle Scholar
• 184. Chiang KC, Kuo SF, Chen CH et al. MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential. Cancer Lett. 369(1), 76–85 (2015).
  Medline CASGoogle Scholar