Extracellular Matrix Stiffness Regulates Cancer Stemness in Uveal Melanoma via the PIEZO1-DOT1L Axis.

ABSTRACT:

Purpose

Cancer stemness drives aggressive behavior and treatment resistance in uveal melanoma (UM). This study aimed to investigate how mechanical signals from the extracellular matrix (ECM) regulated UM stemness through the piezo-type mechanosensitive ion channel component 1 (PIEZO1)-disruptor of telomeric silencing 1-like (DOT1L) signaling axis.

Methods

PIEZO1 expression was assessed using immunofluorescence in human UM and adjacent normal tissues. Polyacrylamide hydrogel models with tunable stiffness were used to simulate the biomechanical microenvironment in vitro. Stemness was assessed by analyzing colony formation, tumorsphere assays, apoptosis resistance, and expression of the stemness markers NANOG and SOX2. In vivo, ECM stiffness was reduced to examine its effects o

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12716446 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature