PAX3 and FOXD3 Promote CXCR4 Expression in Melanoma

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2015 Jul 25

PMID 26205821

Citations 15

Authors

Jennifer D Kubic

Jason W Lui

Elizabeth C Little

Anton E Ludvik

Sasank Konda

Ravi Salgia

Andrew E Aplin

Deborah Lang

Affiliations

Soon will be listed here.

Abstract

Metastatic melanoma is an aggressive and deadly disease. The chemokine receptor CXCR4 is active in melanoma metastasis, although the mechanism for the promotion and maintenance of CXCR4 expression in these cells is mostly unknown. Here, we find melanoma cells express two CXCR4 isoforms, the common version and a variant that is normally restricted to cells during development or to mature blood cells. CXCR4 expression is driven through a highly conserved intronic enhancer element by the transcription factors PAX3 and FOXD3. Inhibition of these transcription factors slows melanoma cell growth, migration, and motility, as well as reduces CXCR4 expression. Overexpression of these transcription factors drives the production of increased CXCR4 levels. Loss of PAX3 and FOXD3 transcription factor activity results in a reduction in cell motility, migration, and chemotaxis, all of which are rescued by CXCR4 overexpression. Here, we discover a molecular pathway wherein PAX3 and FOXD3 promote CXCR4 gene expression in melanoma.

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