Intracellular pH differentially regulates transcription of metabolic and signaling pathways in normal epithelial cells.

ABSTRACT: Intracellular pH (pHi) dynamics regulate normal cell function, and dysregulated pHi dynamics is an emerging hallmark of cancer (constitutively increased pHi) and neurodegeneration (constitutively decreased pHi). However, the molecular mechanisms by which pHi dynamics regulate cell biology are poorly understood. Here, we discovered that altering pHi in normal human breast epithelial cells triggers global transcriptional changes. We identified 176 genes differentially regulated by pHi, with pHi-dependent genes clustering in signaling and glycolytic pathways. Using various normal epithelial cell models, we showed pH-dependent Notch homolog 1 protein expression, with increased protein abundance at high pHi. This resulted in pH-dependent downstream signaling, with increased Notch homolog 1 sign

SUBMITTER: Romero-Moreno R 

PROVIDER: S-EPMC11489351 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature