Researchers at the University of Liège announced on Apr. 2 that the protein Stard7 plays an unexpected and complex role in the development of intestinal cancers. The study, led by scientists from the GIGA Medical Chemistry Laboratory, reveals that Stard7 influences mitochondrial metabolism and tumor growth in ways not previously understood.
Colon cancer remains one of the most common cancers globally, ranking third in diagnosis frequency and second as a cause of cancer-related deaths. Understanding its underlying mechanisms is critical for developing better treatments. The new research focused on creating mouse models that closely replicate human colon physiology to investigate these mechanisms more precisely.
The team concentrated on Stard7, a protein previously believed to have a minor function as a transporter of certain lipids to mitochondria—the cell's energy producers. By selectively disabling the gene responsible for Stard7 production only in intestinal cells, researchers observed significant effects: "When lacking Stard7, intestinal cells struggle on several fronts at once," said Alain Chariot. "We see that their mitochondria are running at a reduced rate, which reduces their ability to produce energy. In response, cells lacking Stard7 generate more unstable and toxic molecules – free radicals – which can damage DNA and other cellular components."
This stress causes affected cells to alter their fat composition and activate emergency programs involving two regulators: mTORC1 promotes cell growth while ATF4 shifts cellular metabolism toward producing serine—an amino acid favored by cancer cells for growth and resistance.
A key finding from this study is that the effect of Stard7 deficiency varies depending on disease context. "We observed that the effects of Stard7 on cancer vary depending on circumstances," Chariot said. In mouse models simulating inflammation-driven colon cancer (similar to inflammatory bowel diseases), lack of Stard7 reduced tumor formation; however, when modeling typical human colon cancer driven by APC gene mutations, loss of Stard7 accelerated tumor growth.
The research also produced a new animal model with both APC mutation and absence of Stard7 specifically in the intestine—a combination resulting in rapid tumor development similar to patterns seen in human patients' distal colons. Additionally, these mice exhibited gut microbiota profiles resembling those found in colorectal cancer patients.
"Our results show that Stard7 can act as a brake on cancer or, conversely, as an accelerator, depending on the mutational status of tumors," Chariot said. He added this underscores how personalized medicine must consider each tumor's specific characteristics before determining treatment approaches.
