Advances in understanding the role of squalene epoxidase in cancer prognosis and resistance.

Abstract

Recently, there has been burgeoning interest in the involvement of cholesterol metabolism in cancer. Squalene epoxidase (SQLE), as a critical rate-limiting enzyme in the cholesterol synthesis pathway, has garnered attention due to its overexpression in various cancer types, thereby significantly impacting tumor prognosis and resistance mechanisms. Firstly, SQLE contributes to unfavorable prognosis through diverse mechanisms, encompassing modulation of the PI3K/AKT signaling pathway, manipulation of the cancer microenvironment, and participation in ferroptosis. Secondly, directing efforts towards targeting SQLE, via mechanisms such as the PI3K/AKT pathway, presents promising avenues for overcoming resistance to conventional therapies such as endocrine cancer therapy, chemotherapy, immunotherapy, or radiotherapy. Moreover, the effectiveness of SQLE protein inhibitors in impeding cancer progression may either depend directly on SQLE inhibition or function through alternative pathways separate from SQLE. This mini-review offers insights into the intricate mechanisms through which SQLE affects the prognosis and resistance profiles across diverse cancer types, while succinctly elucidating the mechanisms underpinning the anticancer effects of SQLE protein inhibitors. Furthermore, this mini-review underscores the necessity for further investigations into the interplay between SQLE and cancer, proposing potential avenues for future research, with the aim of serving as a reference for exploring the mechanisms governing the role of SQLE in cancer regulation.