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Research advances in the role of protective autophagy in regulating vasculogenic mimicry formation in malignancies such as cholangiocarcinoma / 临床肝胆病杂志
Journal of Clinical Hepatology ; (12): 1882-1884, 2019.
Article in Chinese | WPRIM | ID: wpr-779066
ABSTRACT
Cholangiocarcinoma is a primary malignant tumor derived from the epithelium of the intrahepatic and extrahepatic bile ducts, and vasculogenic mimicry induced by hypoxia and lack of nutrition is a key factor for malignant proliferation, recurrence, and metastasis of cholangiocarcinoma. Previous studies have shown that autophagy maintains cell nutrition metabolism under the condition of a lack of nutrition, and preliminary experiments have confirmed that autophagy was associated with VM in cholangiocarcinoma and there was high expression of PAT4 in cholangiocarcinoma cells; on the basis of these studies, it is pointed out that in cholangiocarcinoma, protective autophagy regulates VM formation by maintaining intracellular metabolic balance and cellular homeostasis. As a nutrient sensor in tumor microenvironment, PAT4 mediates protective autophagy via the PI3K-Akt-mTORC1 signaling pathway to regulate VM formation. Histological, cellular molecular, and in vivo experiments have confirmed that autophagy regulates VM formation by maintaining cell metabolism, stem cell features, and extracellular matrix remodeling, which helps to investigate the signal mechanism for PAT4 mediating autophagy to regulate VM. It is suggested that autophagy is the source of energy and nutrition in cholangiocarcinoma cells under the condition of a lack of nutrition, and PAT4 is the trigger point for autophagy in regulating VM formation. These findings provide new thoughts for the metabolism of cholangiocarcinoma cells and lay a theoretical foundation for antiangiogenic drugs combined with autophagy inhibitors in the treatment of highly aggressive tumors.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Journal of Clinical Hepatology Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Journal of Clinical Hepatology Year: 2019 Type: Article