hMENA is a key regulator in endothelin-1/β-arrestin1–induced invadopodial function and metastatic process

Significance Discovering new targets and novel determinants of metastatic spread is an unmet need in ovarian cancer, which is plagued by high rates of recurrence. Endothelin-1 receptors (ET-1R), belonging to the G-protein–coupled receptor family, represent important targets critically involved in malignant progression. Here we identify a mechanistic link between ET-1R and the actin regulatory protein hMENA/hMENAΔv6 through the specific interaction with the multifunctional protein β-arrestin1 (β-arr1), which initiates signaling cascades as part of the molecular complex crucial for invadopodial maturation and malignant dissemination. Targeting ET-1R by using macitentan, a Food and Drug Administration-approved antipulmonary arterial hypertension drug, can impair the β-arr1–mediated signaling network controlling ovarian cancer progression and therefore represents a therapeutic option for ovarian cancer patients.

hMENA is a key regulator in endothelin-1/β-arrestin1–induced invadopodial function and metastatic process Journal Articles