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Article Dans Une Revue Clinical and Translational Medicine Année : 2024

PROM2 overexpression induces metastatic potential through epithelial‐to‐mesenchymal transition and ferroptosis resistance in human cancers

Justine Paris
Claire Wilhelm
  • Fonction : Auteur
Celeste Lebbé
  • Fonction : Auteur
Mohammed Elmallah
  • Fonction : Auteur
Frédéric Pamoukdjian
  • Fonction : Auteur
Audrey Héraud
  • Fonction : Auteur
Guillaume Gapihan
  • Fonction : Auteur
Aurore van De Walle
van Nhan Tran
  • Fonction : Auteur
Diaddin Hamdan
  • Fonction : Auteur
Clara Allayous
  • Fonction : Auteur
Maxime Battistella
  • Fonction : Auteur
Emmanuel van Glabeke
  • Fonction : Auteur
Kah Wai Lim
  • Fonction : Auteur
Sébastien Roger
  • Fonction : Auteur
Anh Tuan Phan
  • Fonction : Auteur
Guilhem Bousquet

Résumé

Abstract Introduction Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin‐2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio‐target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma. Methods and results Methods and results: We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial‐to‐mesenchymal transition (EMT) marker expression and ferroptosis resistance. This was also found in renal cell carcinoma and triple negative breast cancer patient‐derived xenograft models. Using an oligonucleotide anti‐sense anti‐PROM2, we efficaciously decreased PROM2 expression and prevented metastases in melanoma xenografts. We also demonstrated that PROM2 was implicated in an aggravation loop, contributing to increase the metastatic burden both in murine metastatic models and in patients with metastatic melanoma. The metastatic burden is closely linked to PROM2 expression through the expression of EMT markers and ferroptosis cell death resistance in a deterioration loop. Conclusion Our results open the way for further studies using PROM2 as a bio‐target in resort situations in human metastatic melanoma and also in other cancer types.

Domaines

Cancer
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Dates et versions

hal-04519250 , version 1 (25-03-2024)

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Justine Paris, Claire Wilhelm, Celeste Lebbé, Mohammed Elmallah, Frédéric Pamoukdjian, et al.. PROM2 overexpression induces metastatic potential through epithelial‐to‐mesenchymal transition and ferroptosis resistance in human cancers. Clinical and Translational Medicine, 2024, 14 (3), ⟨10.1002/ctm2.1632⟩. ⟨hal-04519250⟩
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