Sqle-flox Mouse

Sqle, squalene epoxidase, is a key rate-limiting enzyme in cholesterol biosynthesis [2,3,4,5]. It is involved in multiple biological processes. By catalyzing the conversion of squalene to squalene-2,3-epoxide, it is crucial for de novo cholesterol biosynthesis. Cholesterol metabolism, in which Sqle plays a part, is associated with various cellular functions and signaling pathways [1,3,6].

In cancer research, Sqle has been shown to play oncogenic roles. In pancreatic cancer, its inhibition led to squalene accumulation-induced endoplasmic reticulum (ER) stress and apoptosis, while its overexpression promoted cell proliferation, cell cycle progression, and tumor growth in vivo by attenuating ER stress and activating lipid rafts-regulated Src/PI3K/Akt signaling pathway [1]. In bladder cancer, Sqle knockdown inhibited tumor cell proliferation and metastasis through the PTEN/AKT/GSK3β signaling pathway, and P53 was identified as a key molecule in this regulation [2]. In osteosarcoma, silence of Sqle suppressed cell proliferation, migration, and invasion, while overexpression had the opposite effects by activating the TGFβ/SMAD signaling pathway [4].

In conclusion, Sqle is essential for cholesterol metabolism. Through gene-knockout or related functional studies in various cancer models, it has been revealed that Sqle plays significant roles in promoting cancer cell growth, proliferation, and metastasis in pancreatic, bladder, and osteosarcoma cancers. Understanding the function of Sqle provides potential therapeutic targets for these diseases.