期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.639111
关键词
colon cancer; serine metabolism; YAP; USP7; organoid
资金
- Social Development Key Project of Jinhua Science and Technology Planning Project [2019-3-004]
- Jinhua Science and Technology Research Program [2020-3-046]
- Jinhua Science and Technology Program major projects [2020-3-028]
- Public Welfare Technology Research Program of Zhejiang Province [LGF18H160029]
- General Program of Zhejiang Province Natural Science Foundation [LY19H160020]
- Program of Zhejiang Province Natural Science Foundation [LY21H160014]
Metabolic reprogramming, specifically serine metabolism through USP7-regulated YAP activity, plays a crucial role in colon cancer growth. The study suggests VP as a potential new treatment for colon cancer by targeting YAP activity and serine metabolism.
Metabolic reprogramming is a vital factor in the development of many types of cancer, including colon cancer. Serine metabolic reprogramming is a major feature of tumor metabolism. Yes-associated protein (YAP) participates in organ size control and tumorigenesis. However, the relationship between YAP and serine metabolism in colon cancer is unclear. In this study, RNA sequencing and metabolomics analyses indicated significant enrichment of the glycine, serine, and threonine metabolism pathways in serine starvation-resistant cells. Short-term serine deficiency inhibited YAP activation, whereas a prolonged response dephosphorylated YAP and promoted its activity. Mechanistically, USP7 increases YAP stability under increased serine conditions by regulating deubiquitination. Verteporfin (VP) effectively inhibited the proliferation of colon cancer cells and organoids and could even modulate serine metabolism by inhibiting USP7 expression. Clinically, YAP was significantly activated in colon tumor tissues and positively correlated with the expression of phosphoglycerate dehydrogenase (PHGDH) and USP7. Generally, our study uncovered the mechanism by which serine metabolism regulates YAP via USP7 and identified the crucial role of YAP in the regulation of cell proliferation and tumor growth; thus, VP may be a new treatment for colon cancer.
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