Nuclear VCP drives colorectal cancer progression by promoting fatty acid oxidation

• DOI: 10.1073/pnas.2221653120
• Publication Date: 2023-10-03T17:52:39Z
• Authors: Youwei Huang; Fang Wang; Xi Lin; Qing Li; Yuli Lu; Jiayu Zhang; Xi Shen; Jingyi Tan; Zixi Qin; Jiahong Chen; Xueqin Chen; Guopeng Pan; Xiangyu Wang; Yuequan Zeng; Shangqi Yang; Jun Liu; Fan Xing; Kai Li; Haipeng Zhang
• Keywords: Histone deacetylase inhibitor; HDAC1

Fatty acid oxidation (FAO) fuels many cancers. However, knowledge of pathways that drive FAO in cancer remains unclear. Here, we revealed valosin-containing protein (VCP) upregulates to promote colorectal growth. Mechanistically, nuclear VCP binds histone deacetylase 1 (HDAC1) and facilitates its degradation, thus promoting the transcription genes, including rate-limiting enzyme carnitine palmitoyltransferase 1A ( CPT1A ). is an alternative fuel for cells environments exhibiting limited glucose availability. We observed a inhibitor blocked upregulation activity expression triggered by metformin (CRC) cells. Combined prove more effective than either agent alone culture vivo. Our study illustrates molecular mechanism underlying regulation demonstrates potential therapeutic utility combination treatment cancer.