TGF-ß1 fucosylation enhances the autophagy and mitophagy via PI3K/Akt and Ras-Raf-MEK-ERK in ovarian carcinoma.

ABSTRACT

Transforming growth factor-ß, a cell secretion factor of the TGF-ß superfamily, is involved in the regulation of cell proliferation, differentiation, cytoskeleton formation, migration, invasion and other biological behaviors. Autophagy and mitophagy play an important role in tumor progression by regulating self-digestion, and degradation and reuse of cells and mitochondria. In this study, changes in autophagy and mitophagy processes in ovarian cancer cells under TGF-ß1 treatment were detected via Western blot and immunofluorescence, as well as the role of fucosylation modification. Changes in mitochondrial membrane potential in response to TGF-ß1 and fucosylation were detected via immunofluorescence. The effects of TGF-ß1 and its fucosylation on autophagic flux were further determined by transient transfection of cells with Ad-mRFP-GFP-LC3 adenovirus. TGF-ß1 clearly promoted autophagy and mitophagy in ovarian cancer cells. TGF-ß1 fucosylation stimulated these regulatory effects on ovarian cancer cells via modulation of PI3K/Akt and Ras-Raf-MEK-ERK pathways through TAK1. Our collective data support the physiological significance of TGF-ß1 and provide a novel direction for targeted therapy for ovarian cancer.