Zou Hongbo, Wang Shuang, Wang Songtao, Wu Hong, Yu Jing, Chen Qian, Cui Wei, Yuan Ye, Wen Xianmei, He Jian, Chen Lin, Yu Ruilian, Zhang Ming, Lan Haitao, Jin Guoxiang, Zhang Xia, Bian Xiuwu, Xu Chuan
Department of Oncology, The Affiliated Hospital of Southwest Medical University Luzhou 646000, China.
Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China Chengdu 610072, China.
Am J Cancer Res. 2018 May 1;8(5):866-878. eCollection 2018.
The dysregulation of transcription factors plays a vital role in tumor initiation and progression. Sex determining region Y-box 5 (SOX5) encodes a member of the SRY-related HMG-box family of transcription factors involved in the determination of the cell fate and the regulation of embryonic development. However, its functional roles in non-small cell lung cancer (NSCLC) remain unclear. Herein, we report that SOX5 sustains stem-like traits and enhances the malignant phenotype of NSCLC cells. We determine that SOX5 is preferentially expressed by cancer stem-like cells (CSLCs) of human NSCLC. gain- and loss-of-function studies demonstrate that SOX5 promotes self-renewal, invasion and migration in NSCLC cells. Importantly, knockdown of SOX5 potently inhibits tumor growth in a xenograft mouse model. Mechanistically, YAP1 can act as an interacting protein of SOX5 to drive the malignant potential of NSCLC cells. Silencing of YAP1 attenuates the malignant processes in NSCLC cells, which is consistent with the function of SOX5 loss. SOX5 overexpression reverses the attenuated malignant progression in YAP1 knockdown cancer cells. Taken together, these findings identify that SOX5 acts as an oncogenic factor by interacting with YAP1 in NSCLC cells and may be a potential therapeutic target for NSCLC patients.
转录因子的失调在肿瘤的发生和发展中起着至关重要的作用。性别决定区Y盒5（SOX5）编码SRY相关HMG盒转录因子家族的一员，该家族参与细胞命运的决定和胚胎发育的调控。然而，其在非小细胞肺癌（NSCLC）中的功能作用仍不清楚。在此，我们报告SOX5维持干细胞样特征并增强NSCLC细胞的恶性表型。我们确定SOX5在人NSCLC的癌干细胞样细胞（CSLCs）中优先表达。功能获得和功能丧失研究表明，SOX5促进NSCLC细胞的自我更新、侵袭和迁移。重要的是，在异种移植小鼠模型中敲低SOX5可有效抑制肿瘤生长。机制上，YAP1可作为SOX5的相互作用蛋白来驱动NSCLC细胞的恶性潜能。沉默YAP1可减弱NSCLC细胞中的恶性过程，这与SOX5缺失的功能一致。SOX5过表达可逆转YAP1敲低癌细胞中减弱的恶性进展。综上所述，这些发现表明SOX5在NSCLC细胞中通过与YAP1相互作用而作为致癌因子，并且可能是NSCLC患者的潜在治疗靶点。
