RHOJ : contrôle de la résistance à la chimiothérapie

Despite the recent development of new targeted therapies, chemotherapies remain the most frequently used approach to treat patients suffering from advanced cancers. Chemotherapy resistance is one of the main causes of treatment failure resulting into death in cancer patients. It has been suggested that the epithelial-to-mesenchymal transition (EMT), a process by which epithelial cells detach from their neighboring cells and acquire invasive properties, plays a role in the acquisition of resistance to anti-cancer therapy. However, the mechanism by which cancer cells presenting EMT resist to anti-cancer therapy is currently unknown.

In a study published in Nature, Cédric Blanpain (WEL Research Institute – ULB) and his team discovered that a protein named RHOJ allows cancer cells presenting EMT to resist to anti-cancer treatments by stimulating the repair of DNA damage caused by the chemotherapy. The group showed that cancer cells presenting EMT become resistant to chemotherapeutic treatment and that RHOJ expression was particularly high in chemotherapy-resistant cells. They then showed that by silencing RHOJ, cancer cells became sensitive to chemotherapy.  The team then explored the mechanism of action and discovered that RHOJ can activate the DNA damage repair pathway induced by chemotherapy, allowing cancer cells to repair the DNA lesions and escape cell death. 

Reference : Debaugnies et al (2023) Nature, doi.org/10.1038/s41586-023-05838-7

Source : Press release ULB