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Abstract A08: CADM1 is a TWIST1 regulated suppressor of melanoma invasion
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Abstract A08: CADM1 is a TWIST1 regulated suppressor of melanoma invasion

Edward J. Hartsough, Michele B. Weiss, Sheera R. Rosenbaum and Andrew E. Aplin
Cancer research (Chicago, Ill.), v 75(14_Supplement), pp A08-A08
15 Jul 2015
DOI: https://doi.org/10.1158/1538-7445.MEL2014-A08

Abstract

Abstract Melanoma is the deadliest form of skin cancer; however, with early detection prior to metastatic dissemination, patients generally have a good prognosis. Recently, our lab has implicated the transcription factor TWIST1 in the progression of melanoma towards metastasis. In melanoma cells, we found that RAS-RAF-MEK-ERK (ERK1/2 pathway) signaling increases TWIST1 expression, which promotes invasive properties in the dermal microenvironment, at least in part by enhancing levels of the matrix metalloproteinase, MMP1. Other TWIST1-regulated targets are poorly described. In this study, we compared expression-profiling data from cells expressing shRNA against TWIST1 or cells overexpressing TWIST1 in order to identify TWIST1-regulated genes. KEGG and GO analysis revealed that TWIST1 is responsible for regulating a number of genes involved in cellular adhesion. We found that TWIST1 levels inversely correlate with levels of cell adhesion molecule 1 (CADM1, also known as NECL-2, IGSF4, TSLC1, SynCAM). Chromatin immunoprecipitation (ChIP) studies and promoter assays demonstrated that TWIST1 physically interacts with the CADM1 promoter and this is associated with reduced CADM1 levels. Additionally, CADM1 expression is inversely associated with ERK1/2 signaling and TWIST1 expression. Modulation of cellular CADM1 levels did not affect proliferation rates; however, overexpression of CADM1 augmented cell-cell interaction, cell aggregation, and reduced trans-endothelial invasion. Furthermore, exogenous CADM1 inhibited serum-directed migration and invasion through Matrigel-coated Boyden chambers, whereas knockdown of CADM1 was associated with enhanced migratory and invasive properties. Taken together, these data provide evidence that CADM1 is negatively regulated by TWIST1 and may act as a suppressor of melanoma invasion. Citation Format: Edward J. Hartsough, Michele B. Weiss, Sheera R. Rosenbaum, Andrew E. Aplin. CADM1 is a TWIST1 regulated suppressor of melanoma invasion. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A08.

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