| First Author | Zhao Y | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 9909 |
| PubMed ID | 39548107 | Mgi Jnum | J:358443 |
| Mgi Id | MGI:7782138 | Doi | 10.1038/s41467-024-54400-0 |
| Citation | Zhao Y, et al. (2024) High mobility group A1 (HMGA1) promotes the tumorigenesis of colorectal cancer by increasing lipid synthesis. Nat Commun 15(1):9909 |
| abstractText | Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet the high energy and biosynthetic demands required for their proliferation. High mobility group A1 (HMGA1) is a structural transcription factor and frequently overexpressed in human colorectal cancer (CRC). Here, we show that HMGA1 promotes CRC progression by driving lipid synthesis in a AOM/DSS-induced CRC mouse model. Using conditional knockout (Hmga1( big up tri, openIEC)) and knock-in (Hmga1(IEC-OE/+)) mouse models, we demonstrate that HMGA1 enhances CRC cell proliferation and accelerates tumor development by upregulating fatty acid synthase (FASN). Mechanistically, HMGA1 increases the transcriptional activity of sterol regulatory element-binding protein 1 (SREBP1) on the FASN promoter, leading to increased lipid accumulation in intestinal epithelial cells. Moreover, a high-fat diet exacerbates CRC progression in Hmga1( big up tri, openIEC) mice, while pharmacological inhibition of FASN by orlistat reduces tumor growth in Hmga1(IEC-OE/+) mice. Our findings suggest that targeting lipid metabolism could offer a promising therapeutic strategy for CRC. |
