High mobility group A1 (HMGA1) promotes the tumorigenesis of colorectal cancer by increasing lipid synthesis.

Autor: Zhao Y; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Liu MJ; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Zhang L; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Yang Q; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Sun QH; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Guo JR; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Lei XY; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., He KY; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Li JQ; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Yang JY; School of Life Sciences, Henan University, Kaifeng, Henan Province, China., Jian YP; School of Life Sciences, Henan University, Kaifeng, Henan Province, China. yongpingjian123@163.com., Xu ZX; School of Life Sciences, Henan University, Kaifeng, Henan Province, China. zhixiangxu08@gmail.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Nov 15; Vol. 15 (1), pp. 9909. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1038/s41467-024-54400-0
Abstrakt: 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 △IEC ) 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 △IEC 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.
Competing Interests: Competing interests The authors declare no conflict of interest.
(© 2024. The Author(s).)
Databáze: MEDLINE
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