CRB3 regulates contact inhibition by activating the Hippo pathway in mammary epithelial cells

• DOI: 10.1038/cddis.2016.478
• Publication Date: 2017-01-12T13:47:21Z
• Authors: Xiaona Mao; Pingping Li; Yaochun Wang; Zheyong Liang; Jie Liu; Juan Li; Yina Jiang; Gang Bao; Lei Li; Bofeng Zhu; Yu Ren; Xinhan Zhao; Jianmin Zhang; Yu Liu; Jin Yang; Peijun Liu
• Keywords: 0303 health sciences; Membrane Glycoproteins; Contact Inhibition; Intracellular Signaling Peptides and Proteins; Cell Polarity; Membrane Proteins; Apoptosis; Breast Neoplasms; Epithelial Cells; Protein Serine-Threonine Kinases; Phosphoproteins; Cytoskeletal Proteins; Mice; 03 medical and health sciences; Animals; Humans; Original Article; Female; Hippo Signaling Pathway; Mammary Glands, Human; Cell Proliferation

AbstractThe 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.