Endosomal pH is an evolutionarily conserved driver of phenotypic plasticity in colorectal cancer.

ABSTRACT: Dysregulated pH is now recognised as a hallmark of cancer. Recent evidence has revealed that the endosomal pH regulator Na⁺/H⁺ exchanger NHE9 is upregulated in colorectal cancer to impose a pseudo-starvation state associated with invasion, highlighting an underexplored mechanistic link between adaptive endosomal reprogramming and malignant transformation. In this study, we use a model that quantitatively captures the dynamics of the core regulatory network governing epithelial mesenchymal plasticity. The model recapitulated NHE9-induced calcium signalling and the emergence of migratory phenotypes in colorectal cancer cells. Model predictions were compared with patient data and experimental results from RNA sequencing analysis of colorectal cancer cells with stable NHE

SUBMITTER: Prasad H 

PROVIDER: S-EPMC11659597 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature