The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.

Abstract

A plethora of cellular signaling pathways are dysregulated in cancer cells, promoting carcinogenesis and migration. Cholesterol has recently been linked to cancer by several subcellular mechanisms, especially by its involvement in the formation of lipid rafts, which promote oncogenic signaling and cancer cell invasion. Squalene synthase (SQS), a pivotal enzyme in the cholesterol biosynthetic pathway downstream of the molecular target of statins, has drawn attention as a potential therapeutic target in cancer. Being the first enzyme in the pathway solely responsible for sterol formation, SQS presents an appealing approach for studying the explicit role of cholesterol in cancer. In recent years, research has re-focused on SQS inhibitors, which modulate cellular cholesterol levels, ultimately regulating crucial processes for cancer progression. However, the mechanisms through which they exert anticancer activity have not been fully elucidated to date. In this review, we examine the roles of cholesterol, lipid rafts, and SQS in cancer and metastasis, and the potential therapeutic implications of SQS inhibitors.