Oncogenic alteration of the cholesterol synthesis pathway is a recognized mechanism of metabolic adaptation. In the present review, we focus on squalene epoxidase (SE), one of the two rate-limiting enzymes in cholesterol synthesis, retracing its history since its discovery as an antimycotic target to its description as an emerging metabolic oncogene by amplification with clinical relevance in cancer. We review the published literature assessing the association between SE over-expression and poor prognosis in this disease. We assess the works demonstrating how SE promotes tumor cell proliferation and migration, and displaying evidence of cancer cell demise in presence of human SE inhibitors in in vitro and in vivo models. Taken together, robust scientific evidence has by now accumulated pointing out SE as a promising novel therapeutic target in cancer treatment.

Squalene epoxidase as a promising metabolic target in cancer treatment

Cirmena, Gabriella;Franceschelli, Paola;Isnaldi, Edoardo;FERRANDO, LORENZO;De Mariano, Marilena;Ballestrero, Alberto;Zoppoli, Gabriele
2018-01-01

Abstract

Oncogenic alteration of the cholesterol synthesis pathway is a recognized mechanism of metabolic adaptation. In the present review, we focus on squalene epoxidase (SE), one of the two rate-limiting enzymes in cholesterol synthesis, retracing its history since its discovery as an antimycotic target to its description as an emerging metabolic oncogene by amplification with clinical relevance in cancer. We review the published literature assessing the association between SE over-expression and poor prognosis in this disease. We assess the works demonstrating how SE promotes tumor cell proliferation and migration, and displaying evidence of cancer cell demise in presence of human SE inhibitors in in vitro and in vivo models. Taken together, robust scientific evidence has by now accumulated pointing out SE as a promising novel therapeutic target in cancer treatment.
File in questo prodotto:
File Dimensione Formato  
Cirmena et al Cancer Letters 2018.pdf

accesso chiuso

Descrizione: Articolo principale
Tipologia: Documento in versione editoriale
Dimensione 534.08 kB
Formato Adobe PDF
534.08 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/909166
Citazioni
  • ???jsp.display-item.citation.pmc??? 37
  • Scopus 60
  • ???jsp.display-item.citation.isi??? 54
social impact