Role of mTORC2 in CXCL12 and EGF-mediated cell migration in Non-Small Cell Lung Cancer

Abstract

Lung cancer is the leading cause of cancer-related death in both the US and the world.1 There is a one percent 5-year survival rate for stage IV Non-Small Cell Lung Cancer (NSCLC) due to its metastatic tendency.2 Metastasis occurs, in part, due to cell migration. The further we understand the signaling pathways that mediate cell migration, the better it can be treated. mTORC2 is a key mediator in cell migration, CXCL12 can stimulate and induce migration in other cancer types.3 EGF is overexpressed in lung cancer and is found to decrease survival rates.4 We seek to understand the effect of CXCL12 and EGF in mTORC2-mediated cell migration. Ras is shown to have direct interaction with mTORC2 and may also be involved in this migration pathway.5 First, I have shown NSCLC A549 cells migrate in response to CXCL12 and this is an mTORC2 mediated pathway. Second, I have shown that A549 cells migrate in response to EGF and this is also mediated by mTORC2. Third, I have shown that Ras plays a part in A549 cell migration, but is not involved in the CXCL12/mTORC2 proposed pathway. Via these findings we propose a pathway where CXCL12 and EGF stimulate and induce migration in A549 cells.