Mitochondrial Ca²⁺ controls pancreatic cancer growth and metastasis by regulating epithelial cell plasticity.

ABSTRACT: Endoplasmic reticulum to mitochondria Ca²⁺ transfer is important for cancer cell survival, but the role of mitochondrial Ca²⁺ uptake through the mitochondrial Ca²⁺ uniporter (MCU) in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Here, we show that increased MCU expression is associated with malignancy and poorer outcomes in patients with PDAC. In isogenic murine PDAC models, Mcu deletion (Mcu^KO) ablated mitochondrial Ca²⁺ uptake, which reduced proliferation and inhibited self-renewal. Orthotopic implantation of MCU-null tumor cells reduced primary tumor growth and metastasis. Mcu deletion reduced the cellular plasticity of tumor cells by inhibiting epithelial-to-mesenchymal transition (EMT), which contributes to metasta

SUBMITTER: Weissenrieder JS 

PROVIDER: S-EPMC12857258 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature