# Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways

## TL;DR

A new peptide called Catestatin may help treat melanoma by stopping cancer growth and drug resistance.

## Contribution

This is the first study to show Catestatin's role in melanoma and its potential as a therapeutic.

## Key findings

- Catestatin reduced melanoma cell proliferation and metastasis without harming normal cells.
- Catestatin reversed drug resistance in melanoma cells by targeting resistance-related genes.
- Catestatin treatment downregulated pathways linked to melanoma progression like hypoxia and EMT.

## Abstract

Melanoma remains one of the most aggressive and treatment-resistant cancers, emphasizing the need for novel therapeutics. In our current study we report a peptide-based approach as potential therapeutic. Here we report for the first time the involvement of Catestatin (CST) peptide in carcinogenesis, with melanoma identified as unexplored and therapeutically relevant context. The expression and role of CST, a Chromogranin A (CgA)-derived peptide with immunomodulatory and reparative properties in skin injury led us to examine its connection to melanoma. Advancing melanoma stages showed decreased CST expression. CST administration to patient derived cells and melanoma cell lines A375, B16F10, SKMEL28 revealed increased apoptosis, decreased proliferation and metastatic ability of the melanoma cells without affecting cell viability for normal skin fibroblasts. CST reduced growth kinetics and tumor weight in B16F10 derived in vivo melanoma tumors. Transcriptomic analyses of CST-treated human cell line and mouse tumor revealed downregulation of hypoxia, collagen remodeling, epithelial to mesenchymal transition pathways (EMT), stress adaptive responses that are accountable for melanoma progression. In Vemurafenib-resistant A375 cells, CST increased apoptosis and repressed multiple resistance associated genes. These results highlight CST as a promising therapeutic candidate capable of opposing melanoma progression and overcoming resistance to current targeted treatments.