Abstract LB-134: mTORC2 regulates the amount of cell surface receptors via its role in protein processing.

Abstract

Abstract Signals from cell surface receptors can become altered in cancer due to increased receptor levels. Little is known on how abnormal protein production and quality control may contribute to receptor amplification and tumorigenesis. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2) associates with translating ribosomes and is involved in protein processing. Association of mTORC2 with ribosomes is increased in tumor cells with enhanced PI3K signaling. We found that inhibition of mTORC2 decreases the expression of ErbB1 and CD147 in breast cancer cells. Whereas upregulation of ErbB1 (EGFR1) expression and/or signaling is associated with increased proliferation in breast cancer, CD147 (basigin; EMMPRIN) is linked to tumor metastasis. In mTORC2-disrupted cells, ErbB1 and CD147 have defective expression and processing. Glucose-starved breast cancer cells undergo misprocessing of CD147 along with a decreased expression of mature receptors. Our findings suggest that mTORC2 plays a role in receptor processing and could therefore control cell proliferation via regulation of the amount of growth factor receptors in the cell surface. Citation Format: Aixa Navia, Chang-chih Wu, Wonjun Oh, Chou Po-Chien, Michael A. DeStefano, Guy Werlen, Estela Jacinto. mTORC2 regulates the amount of cell surface receptors via its role in protein processing. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-134. doi:10.1158/1538-7445.AM2013-LB-134