RHOV is a Detachment-Responsive Rho GTPase Necessary for Ovarian Cancer Peritoneal Metastasis

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Ovarian cancer spreads via transcoelomic metastasis, a process involving peritoneal fluid dissemination, anoikis resistance, and aggregate formation.
• This metastatic pathway is the primary cause of morbidity and mortality in peritoneal cancer patients.
• The precise mechanisms enabling cancer cells to survive matrix detachment and initiate transcoelomic metastasis are not well understood.

Purpose of the Study:

• To identify key molecular mechanisms driving cancer cell survival after matrix detachment.
• To investigate the role of newly identified genes in transcoelomic metastasis of ovarian cancer.
• To define the function of the Rho GTPase RHOV in peritoneal metastasis.

Main Methods:

• Analysis of a conserved detachment-sensitive gene signature in ascites-derived cancer cell lines.
• Validation of RHOV (a Rho GTPase) upregulation in patient ascites-derived tumor cells.
• Functional studies assessing the impact of RHOV loss on anoikis resistance, aggregate integrity, migration, invasion, and in vivo tumor progression.

Main Results:

• A conserved gene signature activated upon matrix detachment was identified.
• RHOV was found to be a top upregulated transcript in detached cancer cells and patient ascites.
• RHOV loss significantly impaired anoikis resistance, aggregate integrity, migration, invasion, and abolished transcoelomic tumor progression in vivo.
• RHOV was shown to enhance c-Jun signaling and cytoskeletal remodeling.

Conclusions:

• RHOV is a novel, detachment-sensitive Rho GTPase.
• RHOV is a critical regulator of peritoneal metastasis in ovarian cancer.
• Targeting RHOV may offer a therapeutic strategy for preventing ovarian cancer spread.