Machine learning links PDF to cold colorectal cancer

A study using laboratory and animal models found that a process called palmitoylation helps a protein called RNF14 stay stable. This happens because palmitoylation stops the protein from being broken down by a process involving ubiquitin. As a result, RNF14 helps control how cells use fats and supports tumor growth in models of colorectal cancer. The researchers also found an earlier step in this process. An enzyme called GCN5 adds a chemical change called acetylation to a protein called YY1. This increases the activity of a gene called ZDHHC9, which allows RNF14 to undergo palmitoylation. The study used colorectal cancer cells and a mouse model containing transplanted tumors. Its findings therefore apply to experimental models, not to treatment results in people with colorectal cancer.

The researchers focused on palmitoylation at a specific part of RNF14 called cysteine 407. They used a method called adenoviral transduction to introduce either normal RNF14 or a changed version that could not undergo palmitoylation. This allowed them to test how important this specific change was. The study found that palmitoylation helped keep RNF14 stable and supported its role in fat metabolism and tumor growth.

When the researchers reduced the activity of ZDHHC9, RNF14 underwent less palmitoylation, fat metabolism was disrupted, and tumor growth was strongly reduced in the models they tested. Together, these findings support a cause-and-effect relationship between palmitoylation, RNF14 stability and the measured changes in tumor growth within these experimental systems. Tests of protein interactions and chemical modifications identified ZDHHC9, an enzyme in the zinc finger DHHC-type palmitoyltransferase family, as the enzyme that adds the palmitoylation modification to RNF14.

The researchers then investigated why ZDHHC9 levels increased. They found that GCN5 adds an acetylation modification to YY1, which increases the expression of ZDHHC9. Their findings describe a chain of four steps: GCN5 adds acetylation to YY1; activated YY1 increases ZDHHC9 expression; ZDHHC9 adds palmitoylation to RNF14 at cysteine 407; and the more stable RNF14 helps change how cells use fats and supports colorectal cancer growth. The researchers used western blotting to measure protein levels, immunoprecipitation to study how proteins interact, and immunofluorescence to view important features of cells.

The researchers also examined chemical changes that happen to proteins after they are made. They measured RNF14 palmitoylation using an acyl resin-assisted capture assay and tested cell viability, or how well cells survived, using a Cell Counting Kit-8 assay. Together, these methods helped the researchers study how this chemical change was linked to RNF14 stability, fat metabolism, cell survival and tumor behavior.

The authors described their findings as evidence that palmitoylation helps control fat metabolism in colorectal cancer. They suggested that the GCN5–YY1–ZDHHC9–RNF14 pathway could be a possible target for future treatments. However, this research is still at the preclinical stage. The reported evidence does not include a clinical trial in people, patient outcomes, treatment safety data or proof that blocking any part of this pathway would help people with colorectal cancer.

The article was published in Cellular and Molecular Life Sciences on 22 October 2026. It is an open-access, peer-reviewed article made available before the final published version. Further edits may still be made.

Subject of Research: A preclinical study of the GCN5–YY1–ZDHHC9–RNF14 pathway and how it controls fat metabolism and tumor growth in colorectal cancer models.

Article Title: GCN5-mediated acetylation of YY1 enhances ZDHHC9-dependent palmitoylation of RNF14 and promotes colorectal cancer progression

Article References: Li, B.-F., Li, G.-Q., Lv, F.-Y., Li, Q.-H., & Lv, L. (2026). GCN5-mediated acetylation of YY1 enhances ZDHHC9-dependent palmitoylation of RNF14 and promotes colorectal cancer progression. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-026-06493-7

Image Credits: AI Generated

DOI: 10.1007/s00018-026-06493-7

Keywords: colorectal cancer, RNF14 palmitoylation, GCN5, YY1 acetylation, ZDHHC9, fat metabolism, cancer cell lines, mouse xenografts, GCN5-mediated acetylation, increased activity, ZDHHC9-dependent palmitoylation