# GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation

## TL;DR

This study shows that a protein called GPNMB marks a resting state in melanoma cells that helps them spread to other parts of the body.

## Contribution

The study identifies GPNMB as a novel marker of quiescent melanoma cells and links it to metastasis.

## Key findings

- Quiescence in melanoma is a dynamic state accessible to most cells, not a rare subpopulation.
- GPNMB is a marker of quiescent cells found in both primary and metastatic tumors.
- Targeting GPNMB with an antibody-drug conjugate reduces metastasis in melanoma.

## Abstract

Melanoma exhibits high intratumoral heterogeneity, characterized by a diverse population of cells undergoing dynamic transitions between cellular states. These adaptive changes enable melanoma cells to survive in the harsh tumor microenvironment, acquire drug resistance, and metastasize. One such state, quiescence, has been linked to both relapse and drug resistance, but its underlying biology and molecular mechanisms remain poorly understood. Our study challenges the conventional understanding of melanoma quiescence. Contrary to the notion of a rare, unique subpopulation, we demonstrate that quiescence is a highly dynamic state accessible to most, if not all, melanoma cells. This state is exquisitely sensitive to microenvironmental cues. We identify GPNMB as a marker of quiescence, that is expressed in both primary and metastatic tumors. GPNMB-positive cells exhibit a pro-metastatic phenotype and are enriched in metastatic sites, suggesting a potential role for quiescence in tumor dissemination. Our findings position GPNMB as a valuable marker for isolating quiescent melanoma cells and as a potential therapeutic target to tackle metastasis.

Quiescence in melanoma is not a rare and static state but a dynamic and reversible condition accessible to most tumor cells, driven by microenvironmental cues. GPNMB marks this state and associates with prometastatic potential, rendering it into a therapeutic target.

Quiescence in melanoma is a dynamic state, not a rare subpopulation, making most cells vulnerable.GPNMB is identified as a novel marker of quiescent melanoma cells in both primary and metastatic tumors.GPNMB-positive cells exhibit a pro-metastatic phenotype and are enriched at metastatic sites.Targeting GPNMB with an antibody-drug conjugate reduces metastasis, highlighting a promising therapeutic strategy.

Quiescence in melanoma is a dynamic state, not a rare subpopulation, making most cells vulnerable.

GPNMB is identified as a novel marker of quiescent melanoma cells in both primary and metastatic tumors.

GPNMB-positive cells exhibit a pro-metastatic phenotype and are enriched at metastatic sites.

Targeting GPNMB with an antibody-drug conjugate reduces metastasis, highlighting a promising therapeutic strategy.

Quiescence in melanoma is not a rare and static state but a dynamic and reversible condition accessible to most tumor cells, driven by microenvironmental cues. GPNMB marks this state and associates with prometastatic potential, rendering it into a therapeutic target.