Abstract
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.
Highlights
Contact inhibition is a process by which cells stop proliferating when they contact adjacent cells
CRB3 is an important mediator of contact inhibition
We examined CRB3 expression in breast cancer tissues and cells to investigate the role of CRB3 in breast cancer
Summary
Contact inhibition is a process by which cells stop proliferating when they contact adjacent cells. Apical-basal polarity components, the apical polarity determinant Crb, have recently been suggested to regulate Hippo pathway activity in Drosophila.[19] Three apicalbasal polarity complexes have been identified to date, including the CRB (Crumbs) complex (CRB/PATJ/PALS1), PAR complex (PAR3/PAR6/aPKC) and Scribble complex (SCRIB/DLG/LGL) These complexes work together to maintain apical-basal polarity.[20] Mammals have three Crumbs family members (CRB1-3).[21] In Drosophila, Crb directly interacts with the upstream Hippo pathway component Expanded.[22,23,24] In mammals, the depletion of CRB3 leads to increased nuclear localization of YAP/TAZ,[25,26] suggesting that CRB3 is associated with the Hippo pathway. CRB3 acted as an upstream regulator of the Hippo pathway and regulated contact inhibition via Kibra and/or FRMD6
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
