SOX5 interacts with YAP1 to drive malignant potential of non-small cell lung cancer cells

American Journal of Cancer Research

Qian Chen¹  Jing Yu²  Shuang Wang³  Hongbo Zou⁴  Hong Wu⁵  Wei Cui⁶  Songtao Wang⁷ 

[1] Department of Experimental Research, Guangxi Medical University, Nanning 530021, China;Department of Oncology, Chengdu Military General Hospital, Chengdu 610083, China;Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial Peoples Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China;Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China;Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China;Department of Respiratory, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, China;Institute of Pathology and Southwest Cancer Center, Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

关键词: SOX5;    YAP1;    self-renewal;    invasion;    migration;    non-small cell lung cancer;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

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. In vitro 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.

【 授权许可】

CC BY-NC