CRB3 regulates contact inhibition by activating the Hippo pathway in mammary epithelial cells
Xiaona Mao 1,2,3,11 , Pingping Li 1,2,11 , Yaochun Wang 1,2 , Zheyong Liang 1,2 , Jie Liu 1,2 , Juan Li1,2 , Yina Jiang 1 , Gang Bao4 , Lei Li5 , Bofeng Zhu 6 , Yu Ren 7 , Xinhan Zhao 8 , Jianmin Zhang9 , Yu Liu10 , Jin Yang* ,8 and Peijun Liu*,1,2
The loss of contact inhibition is a hallmark of cancer cells.
The Hippo pathway has recently been shown to be an important regulator of contact inhibition, and the cell apical polarity determinant protein CRB3 has been suggested to be involved in Hippo
signalling.
However, whether CRB3 regulates contact inhibition in mammary cells remains unclear, and the underlying mechanisms have not been elucidated. As shown in the present study, CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions. Furthermore, we report for the first time that CRB3 acts as an upstream regulator of the Hippo pathway to regulate contact inhibition by recruiting other Hippo molecules, such as Kibra and/or FRMD6, in
mammary epithelial cells. In addition, CRB3 inhibits tumour growth in vivo.
Collectively, the present study increases our understanding of the Hippo pathway and provides an important theoretical basis for exploring new avenues for breast cancer treatment.doi:10.1038/cddis.2016.
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CRB3 regulates contact inhibition by activating the Hippo pathway in
mammary epithelial cells
Article in Cell Death and Disease · January 2017
DOI: 10.1038/cddis.2016.478
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