Abstract LB-307: Giα proteins exhibit functional differences in activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background In a classic model, Giα proteins, Gi1α, Gi2α and G3α, are important for transducing signals from Gi protein-coupled receptors (GPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Giα proteins are also important for activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of Giα proteins in activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether Giα proteins are also engaged in activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of Giα proteins in breast cancer remains to be elucidated. Results We found that Giα deficient MEFs showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Giα1/2/3 knockdown breast cancer cells exhibited a similar defect in this activation and a defect in in vitro growth and invasion. Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1's interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion. Citation Format: Wen-Ming Chu. Giα proteins exhibit functional differences in activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-307. doi:10.1158/1538-7445.AM2014-LB-307