ROLE OF CD151 IN EPIDERMAL GROWTH FACTOR-INDUCED NON-SMALL CELL LUNG CANCER CELL PROLIFERATION

Abstract

Lung cancer, in particular, non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths in Singapore and worldwide. CD151 is the first member of the transmembrane 4 superfamily of cell-surface proteins identified to be a positive effector of tumor cell metastasis. High expression of CD151 is associated with poor prognosis for patients with NSCLC. However, the fundamental question that remains largely unanswered is what factor(s) are likely to increase its expression. By identifying factor(s) that influence CD151 overexpression in NSCLC cells, we can generate potent inhibitors that can interrupt this pathway so as to develop novel approaches for lung cancer treatment. We show for the first time that various factors that are associated with NSCLC prognosis or progression, in particular, EGF, can upregulate CD151 protein expression in not only three NSCLC cell lines, but also in colon and breast cancer cell lines. Importantly, we show that upregulation of CD151 is functionally relevant as it is required for EGF-induced cell proliferation, possibly via the Akt and ERK1/2 pathways.