| Autor: |
Meng Tang, Hui Xu, Hongyan Huang, Hao Kuang, Chenxi Wang, Qinqin Li, Xin Zhang, Yizhong Ge, Mengmeng Song, Xi Zhang, Ziwen Wang, Chaobing Ma, Jinlin Kang, Wanfang Zhang, You Wang, Bo Zhang, Xiaowei Zhang, Yongbing Chen, Minghua Cong, Gerry Melino, Xiaobin Wang, Fuxiang Zhou, Qiang Sun, Hanping Shi |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Advanced Science, Vol 9, Iss 29, Pp n/a-n/a (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202201992 |
| Popis: |
Abstract Although targeting cancer metabolism is a promising therapeutic strategy, clinical success depends on accurate molecular and metabolic subtyping. Here, this study reports two metabolism‐based molecular subtypes associated with the ketogenic treatment of colon cancer: glycolytic (glycolysis+/ketolysis−) and ketolytic (glycolysis+/ketolysis+), which are manifested by distinct profiles of metabolic enzymes and mitochondrial dysfunction, and by different responses to ketone‐containing interventions in vitro and in vivo. Notably, the glycolytic subtype is able to be transformed into the ketolytic subtype in p53‐mutated tumors upon glucose limitation, rendering resistance to ketogenic therapy associated with upregulation of ketolytic enzymes, such as OXCT1 by mutant p53. The allosteric activator of mutant p53 effectively blocks the rewired molecular expression and the reprogrammed metabolism, leading to the suppression of tumor growth. The findings highlight the utility of metabolic subtyping to guide ketogenic therapy in colon cancer and identify mutant p53 as a synthetic lethality target for ketogenic treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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