BioProject

We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1‘s robust effects on melanoma cell invasion, metastasis and tumorigenicity. More...

We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1‘s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGFβ signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1’s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGFβ activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors. Overall design: The HOXA1-induced transcription analysis was conducted using RNAs extracted from SkMel30 cells transduced with either control or HOXA1, followed by hybridization of labeled cDNA onto Affymetrix GeneChips (Human Genome U133Plus2.0). Less...