MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation.

ABSTRACT: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment that commonly support cancer development and progression. Here we show that different cancer cells transfer mitochondria to fibroblasts in cocultures and xenograft tumors, thereby inducing protumorigenic CAF features. Transplantation of functional mitochondria from cancer cells induces metabolic alterations in fibroblasts, expression of CAF markers and release of a protumorigenic secretome and matrisome. These features promote tumor formation in preclinical mouse models. Mechanistically, the mitochondrial transfer requires the mitochondrial trafficking protein MIRO2. Its depletion in cancer cells suppresses mitochondrial transfer and inhibits CAF differentiation and tumor growth. The clinical relevance of

SUBMITTER: Cangkrama M 

PROVIDER: S-EPMC12559006 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature