Abstract:Abstract Targeting the ErbB3-ErbB2 pathway increases the efficacy of MEK inhibitors in melanoma. Given the inter- and intratumor heterogeneity of melanoma, identifying biomarkers for cells within tumo...Abstract Targeting the ErbB3-ErbB2 pathway increases the efficacy of MEK inhibitors in melanoma. Given the inter- and intratumor heterogeneity of melanoma, identifying biomarkers for cells within tumors that will respond effectively to MEK inhibitor-anti-ErbB3 cotargeting is crucial. To this end, we sought to identify transcriptional regulators of ErbB3. Several transcription factors (TFs) are predicted to bind to the promoter region of ErbB3. Using correlation analysis, SOX10 was positively correlated with ErbB3 expression in the RNA-seq data from TCGA cutaneous melanoma dataset. By contrast, an inverse correlation existed between SOX10 and other receptor tyrosine kinases, EGFR and PDGFR, which have been associated with a slow-growing phenotype and resistance to BRAF and MEK inhibitors. siRNA and CRISPR knockdown/out experiments confirmed that SOX10 positively regulates ErbB3 but negatively regulates PDGFR, suggesting plasticity between SOX10-positive and SOX10-negative populations with regard to RTK expression. Overall, this study suggests that SOX10 is a potential biomarker of responsiveness to MEK inhibitor plus ErbB3 targeting antibody in melanoma. Citation Format: Claudia Capparelli, Timothy Purwin, Andrew Aplin. Sox10 differentially regulates receptor tyrosine kinase expression in melanomas [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B05.Read More
Publication Year: 2020
Publication Date: 2020-10-01
Language: en
Type: article
Indexed In: ['crossref']
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