Biochemical and Biophysical Research Communications, Vol.524, No.4, 970-976, 2020
TGF-beta 1 fucosylation enhances the autophagy and mitophagy via PI3K/Akt and Ras-Raf-MEK-ERK in ovarian carcinoma
Transforming growth factor-beta, a cell secretion factor of the TGF-beta 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-beta 1 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-beta 1 and fucosylation were detected via immunofluorescence. The effects of TGF-beta 1 and its fucosylation on autophagic flux were further determined by transient transfection of cells with Ad-mRFP-GFP-LC3 adenovirus. TGF-beta 1 clearly promoted autophagy and mitophagy in ovarian cancer cells. TGF-beta 1 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-beta 1 and provide a novel direction for targeted therapy for ovarian cancer. (C) 2020 Elsevier Inc. All rights reserved.