Intracellular pH dynamics respond to extracellular matrix stiffening and mediate vasculogenic mimicry through β-catenin.

ABSTRACT: Dysregulated intracellular pH (pHi) dynamics and an altered tumor microenvironment have emerged as drivers of cancer cell phenotypes. However, the molecular integration between the physical properties of the microenvironment and dynamic intracellular signaling responses remains unclear. Here, we identify a mechanistic link between ECM stiffness and pHi dynamics in driving vasculogenic mimicry (VM), an aggressive cancer phenotype associated with poor prognosis. We performed single-cell imaging of pHi in lung and breast metastatic cell lines cultured on tunable-stiffness hydrogel systems. We used two tunable-stiffness hydrogel systems to independently model stiffness induced by increased protein secretion (Matrigel) and increased protein crosslinking (Hyaluronic acid gels). We show that incr

SUBMITTER: Lund LM 

PROVIDER: S-EPMC11185592 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature