FAM111B Suppression Enhances Sensitivity to Gemcitabine in Pancreatic Cancer Through Intracellular pH Regulation.

ABSTRACT: Pancreatic cancer remains a highly lethal disease, largely attributed to the rapid development of resistance against standard chemotherapy regimens. Although an acidic tumor microenvironment (TME) has been implicated in this resistance, the molecular mechanisms involved are not fully understood. In this study, we identified Family with Sequence Similarity 111 Member B (FAM111B) as significantly upregulated in pancreatic cancer cells under acidic conditions through RNA sequencing and validated. Functional analyses revealed that FAM111B regulates intracellular pH (pHi). Moreover, combining gemcitabine with α-cyano-4-hydroxycinnamic acid, a lactate transporter inhibitor known to decrease pHi, markedly suppressed pancreatic cancer cell viability compared to gemcitabine alone, thereby enhancing

SUBMITTER: Nishimura M 

PROVIDER: S-EPMC12666461 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature