title: Non-Photoinduced Biological Properties of Verteporfin.
abstract: BACKGROUND
  Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers. However, YAP was also found to be closely connected to autophagy, mitochondria and reactive oxygen/nitrogen species. We herein, review the recent studies where VP was used without photoactivation as a YAP/TEAD inhibitor or protein oligomerization promoter, focusing on its effects on the YAP/TEAD gene targets and other biomarkers related to autophagy.
  
  
  RESULTS
  Since the identification of VP as YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the new potential of this molecule in different cancers, where YAP is overexpressed. However, detailed structural information about its interaction with YAP is still lacking. Concomitantly, VP was identified as autophagosome inhibitor by promoting oligomerization of p62. Moreover, VP proves to be tumor-selective proteotoxic (by oligomerization of p62, STAT3) in colorectal cancer. Knowledge on the biological properties of the only YAP inhibitor available to date is vital for its pharmacological use on cellular and animal models.
  
  
  CONCLUSIONS
  VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.
authors.forename: Floriane
authors.initials: F
authors.lastname: Gibault
authors.forename: Matthieu
authors.initials: M
authors.lastname: Corvaisier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bailly
authors.forename: Guillemette
authors.initials: G
authors.lastname: Huet
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
authors.affiliation: Faculté des Sciences Pharmaceutiques et Biologiques, 3, rue du Professeur Laguesse, BP 83 59006 Lille Cedex, France. philippe.cotelle@inserm.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Cotelle
mesh_terms: D000818:Animals; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D000077362:Verteporfin
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin