Untreated A375 cells vs BRAFi/MEKi-treated A375 cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Skin
SUBMITTER: 
Vanessa Masson
LAB HEAD: Damarys Loew
PROVIDER: PXD068007 | Pride | 2026-06-18
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 20250806_111639_LucillaFabbri-20250401-2conditions.sne | Other | |||
| DesignPRIDE.xlsx | Xlsx | |||
| VBL1660.raw | Raw | |||
| VBL1662.raw | Raw | |||
| VBL1664.raw | Raw |
Items per page: 5 1 - 5 of 8 |
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Project description:The majority of BRAFV600 mutant melanomas regress in response to BRAF/MEK inhibitors (BRAFi/MEKi). Yet nearly all relapse within the first two years. Most BRAFi/MEKi-resistant tumors are cross-resistant to immunotherapies, highlighting the need to prevent and circumvent resistance. We recently showed that androgen receptor (AR) activity is required for sustained melanoma cells proliferation and tumorigenesis. Here we find that AR expression is markedly increased in BRAFi resistant melanoma cells as well as in sensitive cells already at very early times of BRAFi exposure. Proliferation and tumorigenicity of BRAFi resistant melanoma cells are blunted by genetic or pharmacologic suppression of AR activity, while AR overexpression is by itself sufficient to rendersmelanoma cells BRAFi/MEKi-resistant. Increased AR elicits transcriptional changes linked with AXL-positive BRAFi resistant subpopulations and induces expression of PAI-1 and EGFR, two determinants of melanoma progression that associate with elevated AR expression in clinical cohorts. Our results point to increased AR signaling as a determinant of melanoma BRAFi resistance, which can be counteracted by AR as well as PAI-1 and EGFR inhibitors.
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