A new study led by researchers at the University of Liège highlights the unexpected role of Stard7 in the development of intestinal cancers. Long seen as a transporter of some lipids to mitochondria, Stard7 now appears to be a key player in mitochondrial metabolism and tumour development in the intestine.
Colon cancer is one of the most common cancers worldwide: it is the third most frequently diagnosed and the second leading cause of cancer-related deaths. Despite the progress made in recent years, mechanisms that trigger and fuel this disease remain only partially understood. To make some progress in this field of research, scientists need experimental mouse models that accurately replicate human physiology. This is precisely what researchers at the GIGA Medical Chemistry Laboratory at ULiège have set out to do.
Their focus has been on Stard7, a protein whose role, so far, was thought to be relatively minor: it transports some lipids to mitochondria, those tiny structures found in every cell and often defined as power stations, as they produce the energy the cell needs to properly function. Without this supply of lipids, the mitochondria cannot maintain their structure and are not functional.
To explore the role of Stard7 in greater details, the researchers developed models in which the gene that produces this protein was ‘switched off’ only in cells that make up our intestine, without affecting any other organs. This precise experimental approach enabled them to explore the exact consequences of Stard7 deficiency in the intestine. "When lacking Stard7, intestinal cells struggle on several fronts at once," explains 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.”
Faced with this stress, the cell reorganises itself. It alters its fat composition and activates an emergency programme driven by two key regulators. The first one, mTORC1, promotes cell growth, which, when activated, prompts cells to multiply. The second, ATF4, is a molecular switch triggered upon stress, which reprogram cells lacking Stard7 towards the production of a specific amino acid, serine. Serine is, in fact, one of the preferred ‘fuels’ for cancer cells to grow and resist attack. All these changes then create a cellular environment conducive to tumour transformation.
One gene, two effects
But the study’s most surprising discovery lies elsewhere. “We observed that the effects of Stard7 on cancer vary depending on circumstances,” the researcher says. In a model, where cancer is driven by chronic inflammation of the intestine – a situation comparable to what can occur in patients with inflammatory bowel diseases – Stard7 deficiency reduces tumour development. In this case, the protein appears to act as a catalyst for the disease, and its absence protects the intestine. But in a second model, which replicates the most common form of human colon cancer (triggered by a defect in a gene called APC, which normally curbs the proliferation of intestinal cells), the opposite scenario occurs: Stard7 deficiency accelerates tumour development. Here, the protein acts as a natural brake, and its disappearance removes that brake."
A new animal model that resembles the human disease
This second configuration has yielded a novel experimental mouse model that harbours both an APC gene mutation and a lack of Stard7 in the intestine. These mice rapidly develop numerous tumours in the distal colon, the part of the colon most commonly affected in humans, making them particularly faithful replicas of the disease seen in patients.
This model has another important feature: its gut microbiota composition resembles that observed in patients with colorectal cancer. This detail is significant as it will enable researchers to explore the link between microbiota imbalance, mitochondrial dysfunction and cancer development—three phenomena whose interactions remain largely to be unravelled. “Our results show that Stard7 can act as a brake on cancer or, conversely, as an accelerator, depending on the mutational status of tumors. This duality serves as a reminder that, before considering any treatment, it is essential to have a precise understanding of the identity of each tumour.”
This new study illustrates one of the major challenges of personalised medicine, which seeks to tailor treatments not to the disease in general, but to each patient and each tumour in particular. By creating a realistic animal model and by deciphering cellular mechanisms involved, this study lays concrete groundwork for a better understanding - and, hopefully one day, for better treatments to cure one of the deadliest cancers of our time.
EMBO Molecular Medicine
The lipid transfer protein STARD7 controls intestinal tumor development in a context-dependent manner
30-Mar-2026