Osteopontin Induces Epithelial-to-Mesenchymal Transitions in Human Lung Cancer Cells via PI3K/Akt and MEK/Erk1/2 Signaling Pathways

Abstract

SESSION TITLE: Mechanisms of Lung Cancer SESSION TYPE: Original Investigation Slide PRESENTED ON: Saturday, April 16, 2016 at 02:15 PM - 03:45 PM PURPOSE: A multifunctional protein known as Osteopontin (OPN) has an important, yet poorly understood role in Non-Small Cell Lung Cancer (NSCLC) pathogenesis. OPN was reported to be associated with the epithelial-to-mesenchymal transition (EMT) of cells, promoting tumor cells metastasis, but its mechanism remains unclear. METHODS: The present study investigates genetic variations, molecular functions, and/or biological processes of chromosome 4 genes between subtypes of lung cancer, all-the-while investigating patient survival rate of the selected target gene OPN. mRNA and protein expression of OPN, Vimentin, and E-cadherin were further validated in NSCLC tumors and their adjacent non-tumorous lung tissues, using immunohistochemistry in tissue microarray consisting of 208 cases of NSCLCs. RESULTS: We found that OPN and Vimentin overexpressed in NSCLC tissues and negatively correlated with E-cadherin expression. Furthermore, higher levels of OPN were correlated with lymph node metastasis, postoperative recurrence, or distal site metastasis in NSCLC patients. OPN-induced EMT was accompanied with increased cell proliferation and migration, through Akt and Erk1/2 signaling pathways. Interference to OPN expression resulted in the impaired proliferation and movement of lung cancer cells and the up-regulated expression of E-cadherin protein. Silencing of OPN in mouse xenograft models of human lung cancer significantly inhibited tumor growth. CONCLUSIONS: Our data indicate that OPN may serve as a switch during EMT which could be initiated by an autocrine mechanism or through PI3K/Akt and MAPK/Erk1/2 signaling pathways. CLINICAL IMPLICATIONS: OPN can be a potential prognostic marker to screen patients for unfavorable prognosis, which can be important for future clinical applications and represent a revolution in the target therapy for lung cancer. DISCLOSURE: The following authors have nothing to disclose: Lin Shi, Lin Wang, Xiang Wang No Product/Research Disclosure Information