mTOR Directs Breast Morphogenesis through the PKC-alpha-Rac1 Signaling Axis

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The protein kinase mTOR is frequently activated in breast cancers, where it enhances cancer cell growth, survival, and metastastic spread to distant organs. Thus, mTOR is an attractive, clinically relevant molecular target for drugs designed to treat metastatic breast cancers. However, mTOR exists in two distinct complexes, mTORC1 and mTORC2, and the relative roles of each complex have not been elucidated. Moreover, as pathways that regulate normal tissue growth and development are often highjacked to promote cancer, understanding mTOR function in normal mammary epithelial development will likely provide insight into its role in tumor progression. In this study, we assessed the role of mTORC1 and mTORC2 complexes in normal mammary epithelial cell branching, survival, and invasion. Interestingly, while mTORC1 was not required for branching, survival and invasion of mammary epithelial cells, mTORC2 was necessary for these processes in both mouse and human models. Furthermore, we found that mTORC2 exerts its effects primarily through downstream activation of a PKC-alpha-Rac1 signaling axis rather than the more well-studied Akt signaling pathway. Our studies identify a novel role for the mTORC2 complex in mammary morphogenesis, including cell survival and motility, which are relevant to breast cancer progression.

Vyšlo v časopise: mTOR Directs Breast Morphogenesis through the PKC-alpha-Rac1 Signaling Axis. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005291
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005291

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