April 29, 2026
Metastasis is the leading cause of cancer-related deaths, and this is especially true in ovarian cancer, where cancer cells spread beyond the primary tumor into the peritoneal cavity. Stopping metastasis requires a deeper understanding of the molecular events that allow cancer cells to metastasize.
In a recent study published in Cancer Research, Nadine Hempel’s lab led research with collaborators at UPMC Hillman Cancer Center and the University of Alabama at Birmingham, focused on answering the question: what happens to tumor cells in the first minutes to hours after they detach from the primary tumor? Amal Elhaw, a recently graduated PhD student from Hempel’s lab, main author of the study, and now post doc in the Williams lab at Hillman, set out to address this question by focusing on the earliest and less-well understood steps of the metastatic cascade.
Using an unbiased screen of detached ovarian cancer cells, the team identified that the atypical and understudied Rho GTPase RHOV is strongly and rapidly induced within minutes of cell detachment. Genetic depletion of RHOV abolished the metastatic capacity of ovarian cancer cells in preclinical models, both in vitro and in vivo.
The team found that RHOV is required for actin cytoskeleton polymerization, a process critical for maintaining cell shape, pro-metastatic signaling, and adaptations to cellular survival in detached conditions. Altogether, this work identified RHOV as a novel detachment-responsive Rho GTPase necessary for ovarian cancer metastasis.
This research demonstrates that select transcriptional changes within the first hours after a cancer cell detaches are key to cancer cell reprogramming for successful metastatic spread. This early window has been largely overlooked, but the findings of the team suggest that it may represent a powerful opportunity for therapeutic intervention.
Research reported in this publication was supported by the National Institutes of Health under awards R01CA242021, R01CA230628, P50CA272218, and P30CA047904. Amal Elhaw was funded in part by a Cancer Biology Program Trainee Award.