| First Author | Yan H | Year | 2024 |
| Journal | Cell Metab | Volume | 36 |
| Issue | 11 | Pages | 2449-2467.e6 |
| PubMed ID | 39471815 | Mgi Jnum | J:358420 |
| Mgi Id | MGI:7781225 | Doi | 10.1016/j.cmet.2024.10.002 |
| Citation | Yan H, et al. (2024) Hexokinase 2 senses fructose in tumor-associated macrophages to promote colorectal cancer growth. Cell Metab 36(11):2449-2467.e6 |
| abstractText | Fructose is associated with colorectal cancer tumorigenesis and metastasis through ketohexokinase-mediated metabolism in the colorectal epithelium, yet its role in the tumor immune microenvironment remains largely unknown. Here, we show that a modest amount of fructose, without affecting obesity and associated complications, promotes colorectal cancer tumorigenesis and growth by suppressing the polarization of M1-like macrophages. Fructose inhibits M1-like macrophage polarization independently of fructose-mediated metabolism. Instead, it serves as a signal molecule to promote the interaction between hexokinase 2 and inositol 1,4,5-trisphophate receptor type 3, the predominant Ca(2+) channel on the endoplasmic reticulum. The interaction reduces Ca(2+) levels in cytosol and mitochondria, thereby suppressing the activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 1 (STAT1) as well as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Consequently, this impedes M1-like macrophage polarization. Our study highlights the critical role of fructose as a signaling molecule that impairs the polarization of M1-like macrophages for tumor growth. |
