The lipid transfer protein STARD7 controls intestinal tumor development in a context-dependent manner.
(2026) EMBO Molecular Medicine — (2026)
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- Authors
Maurizy, Chloé 
Chariot, Alain
- Abstract
- The role of phosphatidylcholine transporters such as Stard7 in intestinal cancer development is unknown. To explore this issue, we generated a mouse model lacking Stard7 in intestinal epithelial cells (IECs). Loss of Stard7 impaired mitochondrial Complex I activity, led to a severe metabolic and lipid reprogramming, enhanced mitochondrial ROS production and potentiated an mTORC1/ATF4 signature. As a result, levels of enzymes involved in serine biosynthesis were enhanced in Stard7-deficient IECs. We next assessed the consequences of Stard7 deficiency in both Wnt-dependent tumor initiation and in inflammation-driven tumor development. Strikingly, despite generating similar molecular signatures, Stard7 deficiency inhibited tumor development in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice but promoted Wnt-driven cancer initiation in the intestine. Apc mice lacking Stard7 in IECs developed more tumors in the distal colon as well as a specific microbiota signature. Collectively, our results suggest that the genetic status critically controls the effects of Stard7 deficiency on intestinal tumor development.
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Shostak, K., Chen, Y., Maurizy, C., Rademaker, G., Xu, X., Blomme, A., Close, P., Renson, O., Van Hul, M., Cani, P., Klein, S., Florin, A., Büttner, R., Cataldo, D., Delvenne, P., Nemazanyy, I., Wathieu, C., Hego, A., Ormenese, S., et al. (2026). The lipid transfer protein STARD7 controls intestinal tumor development in a context-dependent manner. EMBO Molecular Medicine. Accepted/in-press. https://doi.org/10.1038/s44321-026-00409-5 (Original work published 2026)