PDK1 promotes ovarian cancer metastasis by modulating tumor-mesothelial adhesion, invasion, and angiogenesis via α5β1 integrin and JNK/IL-8 signaling.

ABSTRACT: Ovarian cancer is the most lethal gynecological malignancies owing to the lack of definitive symptoms until development of widespread metastases. Identification of novel prognostic and therapeutic targets is therefore an urgent need to improve survival. Here, we demonstrated high expression of the mitochondrial gatekeeping enzyme, pyruvate dehydrogenase kinase 1 (PDK1), in both clinical samples and cell lines of ovarian cancer. PDK1 expression was significantly associated with metastasis, reduced chemosensitivity, and poor overall and disease-free survival, and further highlighted as an independent prognostic factor. Silencing of PDK1 retarded lactate production, ovarian cancer cell adhesion, migration, invasion, and angiogenesis, and consequently metastasis, concomitant with decreased α5β

SUBMITTER: Siu MKY 

PROVIDER: S-EPMC7028730 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature