AUTHOR=Chen Baoyu , Yuan Yibiao , Sun Lina , Chen Junliang , Yang Mengzhu , Yin Yongmei , Xu Yong 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00832

DOI=10.3389/fcell.2020.00832

ISSN=2296-634X

ABSTRACT=<p>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 <italic>trans</italic>-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 <italic>in vitro</italic> and metastasis <italic>in vivo</italic>. 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.</p>