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

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  • 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.


  • Di Modugno, Francesca
  • Caprara, Valentina
  • Chellini, Lidia
  • Tocci, Piera
  • Spadaro, Francesca
  • Ferrandina, Gabriella
  • Sacconi, Andrea
  • Blandino, Giovanni
  • Nisticò, Paola
  • Bagnato, Anna
  • Rosanò, Laura

publication date

  • March 20, 2018