Shengjing Hospital of China Medical University, China.
Shengjing Hospital of China Medical University, China.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):970-976. doi: 10.1016/j.bbrc.2020.02.028. Epub 2020 Feb 12.
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.
转化生长因子-β（TGF-β）是 TGF-β 超家族的一种细胞分泌因子，参与细胞增殖、分化、细胞骨架形成、迁移、侵袭等生物学行为的调节。自噬和线粒体自噬通过调节细胞和线粒体的自我消化、降解和再利用，在肿瘤进展中发挥重要作用。本研究通过 Western blot 和免疫荧光检测 TGF-β1 处理卵巢癌细胞后自噬和线粒体自噬过程的变化，以及岩藻糖基化修饰的作用。通过免疫荧光检测 TGF-β1 和岩藻糖基化对线粒体膜电位的影响。通过瞬时转染 Ad-mRFP-GFP-LC3 腺病毒进一步确定 TGF-β1 及其岩藻糖基化对自噬流的影响。TGF-β1 明显促进卵巢癌细胞的自噬和线粒体自噬。TGF-β1 岩藻糖基化通过 TAK1 调节 PI3K/Akt 和 Ras-Raf-MEK-ERK 通路，刺激这些对卵巢癌细胞的调节作用。我们的综合数据支持 TGF-β1 的生理意义，并为卵巢癌的靶向治疗提供了新的方向。
