SE (also called squalene epoxidase or squalene monooxygenase, SM EC 1.14.99.7) is a 64 kDa enzyme codified by Human SQLE gene. It was first detected in rat liver microsomes, in 1969. SE is located in the endoplasmic reticulum of cells, and although ubiquitous, it is present at very low levels in most non-cholesterolemic mammalian tissues, while it is highly expressed in liver, neural tissue, in the gut, and in the skin.

    Oncogenic alteration of the cholesterol synthesis pathway is a recognized mechanism of metabolic adaptation. SE is a rate-limiting enzyme leading to effective inhibition of cholesterol synthesis when blocked: if the step of squalene oxygenation catalyzed by SE is influenced, the synthesis of sterols and cell membrane or even cell growth will be subsequently affected. In addition to this transcriptional regulation, the rapid shutdown of cholesterol synthesis requires post-transcriptional control: SE is directly regulated by cholesterol itself which results in its degradation via the ubiquitin-proteasome system.

    High expression of SQLE has been implicated in lethal prostate cancer pathogenesis, in colorectal cancer, and in squamous lung cancer occurrence and development. In that context, SQLE has been suggested as a new molecular marker predicting poor prognosis. Finally, a recent study suggests the involvement of SE in leukemia. In particular, approximately threefold-higher SQLE transcript levels were observed in the daunorubicin-resistant leukemia CEM/R2 cell line.

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