The Ca²⁺ channel Orai3 drives gemcitabine resistance in pancreatic cancer through NFATc1-dependent SLIT3 expression.

ABSTRACT: Pancreatic Cancer (PC) is one of the most aggressive cancers and is associated with poor prognosis. One of the routinely used chemotherapeutic drugs for the treatment of advanced PC is gemcitabine, which offers survival benefits to patients. However, acquired gemcitabine resistance leads to recurrence and metastasis, and the long-term prognosis remains poor. Although there is substantial clinical evidence of gemcitabine resistance, the cellular and molecular mechanisms that drive this resistance remain largely unappreciated. Here, we reveal that Orai3, a Ca^2+-selective channel, is a crucial inducer of gemcitabine resistance. We demonstrate that Orai3 is overexpressed and hyperfunctional in gemcitabine-resistant PC cells. Orai3 silencing in gemcitabine-resistant cells enhances ch

SUBMITTER: Arora S 

PROVIDER: S-EPMC13625800 | biostudies-literature | 2026 Aug

REPOSITORIES: biostudies-literature