AI Article Synopsis
- An excessive fructose diet is linked to the progression of colorectal cancer (CRC) and its metastasis to the liver, but the specific mechanisms involved are not well understood.
- The study found that fructose absorbed by primary CRC can enhance liver metastasis through increased expression of KHK-A, which facilitates this process by modifying the enzyme PKM2.
- Nuclear accumulation of phosphorylated PKM2, driven by KHK-A, boosts CRC cell migration and resistance to cell death, while targeted treatment with TEPP-46 can inhibit these pro-metastatic effects.
Article Abstract
Excessive fructose diet is closely associated with colorectal cancer (CRC) progression. Nevertheless, fructose's specific function and precise mechanism in colorectal cancer liver metastasis (CRLM) is rarely known. Here, this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM, and the expression of KHK-A, not KHK-C, in liver metastasis was higher than in paired primary tumors. Furthermore, KHK-A facilitated fructose-dependent CRLM and by phosphorylating PKM2 at Ser37. PKM2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of PKM2. EMT and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells' migration ability and anoikis resistance during CRLM progression. TEPP-46 treatment, targeting the phosphorylation of PKM2, inhibited the pro-metastatic effect of KHK-A. Besides, c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A, forming a positive feedback loop.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252482 | PMC |
| http://dx.doi.org/10.1016/j.apsb.2024.04.024 | DOI Listing |
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