Triple-negative breast cancers (TNBC: negative for oestrogen-receptor, progesterone-receptor and human-epidermal-growth-factor receptor 2 [HER2]) account for 15-20% of breast cancers and are characterized by an extremely aggressive phenotype. Currently, there is no efficient targeted therapy that can prevent the metastatic dissemination of TNBC. The serine threonine kinase PKCθ has recently been identified as a potential new marker of TNBC and as a strong inducer of cancer invasion. However, how PKCθ controls tumour invasion in TNBC is still unclear. Here our results suggest that PKCθ can promote invasion by activating the focal adhesion kinase (FAK) signalling that regulates the cycle of focal contact formation and disassembly. As a consequence of this activation, PKCθ enhances the dynamic of adhesion turnover, Rho GTPases activity and protrusions formation. We also have unravelled the molecular mechanisms by which PKCθ controls FAK: PKCθ interacts with and phosphorylates FAK thus leading to its opening and activation. We believe that the identified phosphorylation sites are implicated in the PKCθ controlled invasion. In the long term, this study could help develop new targeted therapy for TNBC such as PKCθ specific inhibitors that would limit metastasis formation.
Citation Format: Lucie Chadelle, Valérie Cadamuro, Jiaying Liu, Xiaobo Wang, Karine Belguise. Control of invasion by PKC theta in triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B59.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.