Publication in EMBO Molecular Medicine
Stard7, a key and context-dependent player in colon cancer
Alain Chariot’s team has just published a study in EMBO Molecular Medicine shedding light on the unexpected role of the Stard7 protein in the development of intestinal cancers. Long regarded as a simple lipid transporter, Stard7 now emerges as a key player in mitochondrial metabolism and tumor initiation in the intestine.
Colon cancer is the third most common cancer and the second leading cause of cancer-related death. It is therefore important to generate experimental models that faithfully mimic the human disease.
To understand the function of the Stard7 protein, the researchers developed several mouse models in which the corresponding gene is specifically inactivated in intestinal epithelial cells. This loss of function profoundly disrupts cellular metabolism, leading to reduced mitochondrial complex I activity, increased oxidative stress, lipid reprogramming, and activation of an mTORC1/ATF4 signature that ultimately stimulates serine biosynthesis. These are all dysregulations associated with tumor growth.
The study, however, reveals a major finding: the effects of Stard7 on tumor formation depend on the genetic context. In an inflammation-induced cancer model (AOM/DSS), the absence of Stard7 reduces tumor formation. By contrast, in a context where the Wnt pathway is constitutively activated, as is the case in most human colon cancers, loss of Stard7 accelerates tumor onset.
The researchers therefore created a new mouse model, the Apc+/Min/Stard7ΔIEC mice, which develop numerous tumors in the distal colon, a location that closely mirrors human disease. This model also displays a microbiota signature identical to that observed in patients with colorectal cancer. It therefore represents a particularly relevant tool for studying the links between the microbiota, mitochondrial metabolism, and colon cancer.
“Our results show that Stard7 can act either as a tumor suppressor gene or, conversely, as an oncogenic factor depending on the mutational context. This duality highlights the importance of precisely understanding the genetic context of intestinal tumors before considering any therapeutic approach,” explains Alain Chariot (WELRI Investigator), who led the study.
This work opens the door to new strategies for modeling, understanding, and potentially targeting colorectal cancers, particularly those dependent on the Wnt pathway and influenced by the intestinal microbiota.
Reference
Kateryna Shostak, Yu Chen, Chloé Maurizy, Gilles Rademaker, Xinyi Xu, Arnaud Blomme, Pierre Close, Olivier Renson, Matthias Van Hul, Patrice D Cani, Sebastian Klein, Alexandra Florin, Reinhard Büttner, Didier Cataldo, Philippe Delvenne, Ivan Nemazanyy, Caroline Wathieu, Alexandre Hego, Sandra Ormenese, Olivier Peulen, Marc Thiry, Roopesh Krishnankutty, Jair Marques Jr, Alex von Kriegsheim & Alain ChariotEMBO Molecular Medicine, March 30thContact
Published on 3/30/26
