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. | Zhao et al. Genome Biology 2018 19 35 https s13059-018-1412-6 RESEARCH Open Access The RNA binding protein SORBS2 suppresses metastatic colonization of ovarian cancer by stabilizing tumor- suppressive immunomodulatory transcripts Linjie Zhao1 Wei Wang2 Shuang Huang1 Zhengnan Yang1 Lian Xu3 Qilian Yang1 Xiu Zhou1 Jinjin Wang4 Qiuhong Shen1 Chenlu Wang4 Xiaobing Le1 Min Feng3 Nianxin Zhou1 Wayne Bond Lau5 Bonnie Lau6 Shaohua Yao1 Tao Yi1 Xin Wang2 Xia Zhao1 Yuquan Wei1 and Shengtao Zhou1 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
