Transforming growth factor-β, a cell secretion factor of the TGF-β 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-β1 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-β1 and fucosylation were detected via immunofluorescence. The effects of TGF-β1 and its fucosylation on autophagic flux were further determined by transient transfection of cells with Ad-mRFP-GFP-LC3 adenovirus. TGF-β1 clearly promoted autophagy and mitophagy in ovarian cancer cells. TGF-β1 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-β1 and provide a novel direction for targeted therapy for ovarian cancer.
Copyright © 2020 Elsevier Inc. All rights reserved.

Author