# Calcium Dysregulation Promotes Glioma Progression by Inhibiting STAT3 Degradation Through Blocking Chaperone‐Mediated Autophagy

## TL;DR

Calcium imbalance in brain tumors promotes cancer growth by preventing the breakdown of a key protein called STAT3 through a specific cellular process.

## Contribution

The study identifies TRPC1 as a novel regulator of STAT3 stability via chaperone-mediated autophagy in gliomas.

## Key findings

- TRPC1 increases STAT3 protein levels, promoting glioma cell migration.
- TRPC1 inhibits chaperone-mediated autophagy, preventing STAT3 degradation.
- TRPC1 modulates the interaction between HDAC6 and HSC70, affecting CMA activity.

## Abstract

Calcium dysregulation is closely associated with cancer cell proliferation, migration, and invasion. Transient receptor potential canonical 1 (TRPC1) plays an essential role in regulating calcium homeostasis. However, the role of TRPC1 in calcium dysregulation in gliomas remains incompletely understood. In this study, we demonstrate that TRPC1 promotes glioma cell migration by increasing Signal transduction and transcription activator 3 (STAT3) protein levels. Furthermore, we show that TRPC1 modulates STAT3 stability by inhibiting chaperone‐mediated autophagy (CMA), and we identify STAT3 as a novel substrate of CMA. Additionally, TRPC1 modulates the interaction between HDAC6 and Heat Shock Cognate 70 through intracellular Ca2+ homeostasis, which is associated with changes in CMA activity. These changes prevent STAT3 degradation, highlighting the TRPC1‐HDAC6 axis as a regulator of glioma progression. Thus, the TRPC1‐HDAC6 axis inhibits STAT3 degradation by suppressing CMA activity, contributing to glioma progression. This pathway may represent a potential therapeutic target.