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PI3K in cancer: its structure, activation modes and role in shaping tumor microenvironment

    Xiaoyan Liu

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    Authors contributed equally

    Search for more papers by this author

    ,
    Yan Xu

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    Authors contributed equally

    Search for more papers by this author

    ,
    Qing Zhou

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    ,
    Minjiang Chen

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    ,
    Yu Zhang

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    ,
    Hongge Liang

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    ,
    Jing Zhao

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    ,
    Wei Zhong

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    &
    Mengzhao Wang

    *Author for correspondence: Tel.: +86 69156114;

    E-mail Address: drwang_pumch@sina.com

    Department of Pulmonary Medicine, Lung Cancer Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, PR China

    Published Online:https://doi.org/10.2217/fon-2017-0588

    The role of PI3K in cancer has been well established, and mutations of PIK3CA, the gene coding for catalytic subunit p110α of PI3K, are found in approximately 30% human cancers. The hyperactivated PI3K pathway plays a central role in the tumor cell activities such as proliferation, differentiation, chemotaxis, survival, trafficking and metabolism. Besides, PI3K pathway is involved in the regulation of angiogenesis and the host immune response against cancer. Therefore, the inhibition of PI3K pathway can yield multifaceted tumor cell-extrinsic effects that may synergize with chemotherapy, and more importantly, with the newly revived immunotherapy. Here, we review the structures and activation modes of PI3Ks and its implications in angiogenesis, extracellular matrix remodeling and tumor immunity.

    Papers of special note have been highlighted as: • of interest

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