Prkci promotes colorectal cancer metastasis by phosphorylating and stabilizing Tgfbr1 to activate TGF-β signaling.

ABSTRACT: Colorectal cancer is one of the most common malignancies worldwide, with metastasis being the leading cause of cancer-related mortality. However, the molecular mechanisms driving CRC metastasis remain poorly understood. In this study, we identified Prkci as a critical oncogenic driver in CRC metastasis. Prkci was significantly upregulated in metastatic CRC tissues. Mechanistically, Prkci phosphorylated and stabilized Tgfbr1, a key receptor in the Transforming Growth Factor Beta signaling pathway, preventing its proteasomal degradation and amplifying downstream signaling cascades. This stabilization promoted epithelial-to-mesenchymal transition, enhancing migratory and invasive capacities of CRC cells. In vivo, Prkci knockout significantly reduced liver and lung metastases and prolonged sur

SUBMITTER: Li P 

PROVIDER: S-EPMC12085833 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature