Lung Cancer: Mechanisms of Lung Cancer |

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

Lin Shi; Lin Wang; Xiang Wang
Author and Funding Information

Zhongshan Hospital, Fudan University Medical School; Shanghai Institute of Clinical Bioinformatics, Shanghai, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A332. doi:10.1016/j.chest.2016.02.345
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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

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