Authors

Linjie Zhao, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Wei Wang, City University of Hong Kong
Shuang Huang, West China Second University Hospital, Sichuan University and Collaborative Innovation CenterFollow
Zhengnan Yang, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Lian Xu, West China Second University Hospital, Sichuan University
Qilian Yang, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Xiu Zhou, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Jinjin Wang, Sichuan University
Qiuhong Shen, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Chenlu Wang, Sichuan University
Xiaobing Le, West China Second University Hospital, Sichuan University and Collaborative Innovation CenterFollow
Min Feng, West China Second University Hospital, Sichuan University
Nianxin Zhou, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Wayne Bond Lau, Thomas Jefferson UniversityFollow
Bonnie Lau, Kaiser Santa Clara Medical Center, Affiliate of Stanford UniversityFollow
Shaohua Yao, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Tao Yi, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Xin Wang, City University of Hong Kong
Xia Zhao, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Yuquan Wei, West China Second University Hospital, Sichuan University and Collaborative Innovation Center
Shengtao Zhou, West China Second University Hospital, Sichuan University and Collaborative Innovation Center

Document Type

Article

Publication Date

3-16-2018

Abstract

BACKGROUND: Ovarian cancer constitutes one of the most lethal gynecologic malignancies for females. Currently, early detection strategies and therapeutic options for ovarian cancer are far from satisfactory, leading to high diagnosis rates at late stages and disease relapses. New avenues of therapy are needed that target key processes in ovarian cancer progression. While a variety of non-coding RNAs have been proven to regulate ovarian cancer metastatic progression, the functional roles of RNA-binding proteins (RBPs) in this process are less well defined.

RESULTS: In this study, we identify that the RBP sorbin and SH3 domain containing 2 (SORBS2) is a potent suppressor of ovarian cancer metastatic colonization. Mechanistic studies show that SORBS2 binds the 3' untranslated regions (UTRs) of WFDC1 (WAP four-disulfide core domain 1) and IL-17D (Interleukin-17D), two secreted molecules that are shown to act as metastasis suppressors. Enhanced expression of either WFDC1 or IL-17D potently represses SORBS2 depletion-mediated cancer metastasis promotion. By enhancing the stability of these gene transcripts, SORBS2 suppresses ovarian cancer invasiveness and affects monocyte to myeloid-derived suppressor cell and M2-like macrophage polarization, eliciting a tumor-suppressive immune microenvironment.

CONCLUSIONS: Our data illustrate a novel post-transcriptional network that links cancer progression and immunomodulation within the tumor microenvironment through SORBS2-mediated transcript stabilization.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

29548303

Language

English

Included in

Oncology Commons

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