Abstract 3882: Identification of targetable EMT markers in cancer stem-like cells derived from therapeutic resistant melanoma

Melanoma is the deadliest form of skin cancer, expected to claim approximately 10,000 lives in 2016. An activating mutation in BRAF(V600E) occurs in 50-60% of melanomas and 7% of all cancers. Despite an unprecedented initial response, patients treated with a highly effective BRAF inhibitor, vemurafenib (FDA approved 2011), acquire drug resistance within 6-9 months. Vemurafenib-resistant sub-lines, derived from BRAFV600E isogenic parental melanoma cells, have altered cell morphology and upregulated PDGFRβ expression. Epithelial-to-mesenchymal transition (EMT), a hallmark of cancer-stem-like cells (CSC), is a potential mechanism that melanomas employ to evade targeted therapy. Through immunocytochemical, immunoblot, and flow cytometric analysis, we investigated the expression profile of EMT biomarkers within parental and resistant melanoma cell lines. Our findings indicate CSCs within melanoma populations may serve as progenitor cells for therapy-resistant melanoma sublines through differential expression of key EMT-related biomarkers. Furthermore, resistant cell lines were significantly more invasive in migration assays. Our results implicate notable EMT biomarkers in CSCs that can be used as novel targets for diagnosis and treatment of tumor resistance in melanoma patients. Citation Format: William P. Crosson, Elyse Berlinberg, Ramin Nazarian. Identification of targetable EMT markers in cancer stem-like cells derived from therapeutic resistant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3882. doi:10.1158/1538-7445.AM2017-3882