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A novel isoform of ATOH8 promotes the metastasis of breast cancer by regulating RhoC
Mengyao Xu1,† , Shan Huang1,2,† , Xiaoli Dong1,† , Yanan Chen1,3 , Miao Li1 , Wen Shi1 , Guanwen Wang1 , Chongbiao Huang4 , Qiong Wang1 , Yanhua Liu1,3 , Peiqing Sun2 , Shuang Yang1 , Rong Xiang1,3 , Antao Chang1,2,3,*
1School of Medicine, Nankai University, Tianjin 300071, China
2Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Medical Center, Winston-Salem, NC 27157, USA
3International Collaborative Innovation Center of Medicine, Nankai University, Tianjin 300071, China
4Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
These authors contributed equally to this work.
*Correspondence to:Antao Chang , Email:anchang@wakehealth.edu
J Mol Cell Biol, Volume 13, Issue 1, January 2021, Pages 59-71  https://doi.org/10.1093/jmcb/mjaa050
Keyword: breast cancer, ATOH8, metastasis, RhoC

Metastases are the main cause of cancer-related mortality in breast cancer. Although significant progress has been made in the field of tumor metastasis, the exact molecular mechanisms involved in tumor metastasis are still unclear. Here, we report that ATOH8-V1, a novel isoform of ATOH8, is highly expressed in breast cancer and is a negative prognostic indicator of survival for patients. Forced expression of ATOH8-V1 dramatically enhances, while silencing of ATOH8-V1 decreases the metastasis of breast cancer cell lines. Moreover, ATOH8-V1 directly binds to the RhoC promoter and stimulates the expression of RhoC, which in turn enhances the metastasis of breast cancer. Altogether, our data demonstrate that ATOH8-V1 is a novel pro-metastatic factor that enhances cancer metastasis, suggesting that ATOH8-V1 is a potential therapeutic target for treatment of metastatic cancers.