Abstract 1432: TORC2 dependent control of cell growth and size in cancer cells

Abstract Severe defects in cell growth and size are a nearly universal feature of cancer cells and have provided a basis for cancer pathology for over 100 years; however, the underlying mechanisms remain largely unknown. Recent work in budding yeast has shown that a highly conserved signaling network surrounding Tor complex 2 (TORC2) controls cell growth and size. A key component of the network is the yeast homolog of serum and glucocorticoid-regulated kinase (SGK), which controls production of ceramide signaling lipids that control cell growth and size. Here, we present evidence that a similar TORC2 network controls cell growth and size in mammalian cells. In addition, we show that expression of oncogenic drivers in NIH3T3 cells causes defects in cell size, as well as defects in TORC2-dependent control of cell size. Cancer cells also show severe defects in TORC2-dependent control of cell size. Our working hypothesis is that the TORC2 network is downstream of multiple oncogenes, and that aberrant TORC2 signaling is a major cause of the nearly universal size defects observed in cancer cells. A better understanding of the mechanisms that control cell growth and size in normal cells, and how they go awry in cancer, could identify new targets for drugs to improve cancer therapies. Citation Format: Jerry T. DeWitt, Douglas Kellogg. TORC2 dependent control of cell growth and size in cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1432.