Abstract A44: S100A4 drives the invasive potential of non-small cell lung cancer cells and is targeted by FDA approved drugs

Abstract

Abstract The metastatic nature of advanced non-small cell lung cancer (NSCLC), often associated with therapeutic resistance, accounts for the majority of cancer death with the 5-year survival rate less than 10%. This dismal outcome will remain the same until we gain better understanding of the crucial drivers of the metastatic process and gain the power to effectively target them. S100A4 is a tumor metastasis associated protein and an epithelial to mesenchymal transition (EMT) marker. S100A4 contributes to several hallmarks of cancer such as anti-apoptosis, proliferation and therapeutic resistance, and has been implicated in the progression of different types of cancer, including breast, colon and pancreatic cancer. However, the impact of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer has not been properly explored. Here, by using established lung cancer cell lines, we demonstrate that S100A4 is upregulated in a subset of lung cancer cell lines both at the mRNA and protein levels. We further found that inhibition of S100A4 by shRNA in A549 and H460 lung cancer cell lines reduced cell proliferation and decreased 3D invasive growth, while exogenous overexpression of S100A4 in H1299 cells increased invasive potential. Interestingly, we showed that Niclosamide, an FDA-approved anti-tapeworm agent, suppressed S100A4 expression in A549 and H358 cells and led to decreased cell proliferation, invasion and invasive growth. Similarly, we found that a CDC25 inhibitor, NSC95397, disrupts the interaction of S100A4 and non-muscle myosin IIA and also decreased A549 cell invasion. Collectively, these data highlight the importance of S100A4 in lung cancer invasion and metastasis and provide the rationale for targeting S100A4 as a potential agent to combat lung cancer. Citation Format: Min Chen, Rachel Stewart, Teresa Knifley, Brittany L. Carpenter. S100A4 drives the invasive potential of non-small cell lung cancer cells and is targeted by FDA approved drugs. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A44.