MKL1 Mediates TGF-β Induced RhoJ Transcription to Promote Breast Cancer Cell Migration and Invasion

Baoyu Chen; Yibiao Yuan; Lina Sun; Junliang Chen; Mengzhu Yang; Yongmei Yin; Yong Xu

doi:10.3389/fcell.2020.00832

MKL1 Mediates TGF-β Induced RhoJ Transcription to Promote Breast Cancer Cell Migration and Invasion

Front Cell Dev Biol. 2020 Aug 25:8:832. doi: 10.3389/fcell.2020.00832. eCollection 2020.

Authors

Baoyu Chen¹, Yibiao Yuan¹, Lina Sun^{2

3}, Junliang Chen⁴, Mengzhu Yang⁵, Yongmei Yin⁵, Yong Xu^{1

3}

Affiliations

¹ Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysioloy and Laboratory Center for Experimental Medicine, Nanjing Medical University, Nanjing, China.
² Department of Pathology and Pathophysiology, College of Life and Basic Medical Sciences, Soochow University, Suzhou, China.
³ Institute of Biomedical Research, Liaocheng University, Liaocheng, China.
⁴ Department of Pathophysiology, Wuxi Medical School, Jiangnan University, Wuxi, China.
⁵ Department of Oncology, First Hospital Affiliated to Nanjing Medical University, Nanjing, China.

Abstract

Differential regulation of gene transcription contributes to cancer metastasis. We investigated the involvement of a Rho GTPase (RhoJ) in breast cancer metastasis focusing on the mechanism underlying RhoJ trans-activation by pro-metastatic cues. We report that expression of RhoJ was up-regulated in malignant breast cancer cells compared to more benign ones. Higher RhoJ expression was also detected in human breast cancer biopsy specimens of advanced stages. RhoJ depletion attenuated breast cancer cell migration and invasion in vitro and metastasis in vivo. The pro-metastatic stimulus TGF-β activated RhoJ via megakaryocytic leukemia 1 (MKL1). MKL1 interacted with and was recruited by ETS-related gene 1 (ERG1) to the RhoJ promoter to activate transcription. In conclusion, our data delineate a novel transcriptional pathway that contributes to breast cancer metastasis. Targeting the ERG1-MKL1-RhoJ axis may be considered as a reasonable approach to treat malignant breast cancer.

Keywords: ERG1; MKL1; RhoJ; breast cancer metastasis; transcription factors; transcriptional regulation.