Abstract:
Cancer has become a serious health burden that results in high incidence and mortality rates every year, mainly due to various molecular alterations inside the cell. Liver X receptors (LXRs) dysregulation is one among them that plays a vital role in cholesterol metabolism, lipid metabolism and inflammation and also plays a crucial role in various diseases such as obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), cardiovascular diseases, Type 2 diabetes, osteoporosis, and cancer. Studies report that the activation of LXRs inhibits cancer growth by inhibiting cellular proliferation, inducing apoptosis and autophagy, regulating cholesterol metabolism, various signalling pathways such as Wnt, and PI3K/AKT, modulating the expression levels of cell-cycle regulators, and promoting antitumor immunity inside the tumor microenvironment. In this review, we have discussed the role, structure, and functions of LXRs and also summarized their ligands along with their mechanism of action. In addition, the role of LXRs in various cancers, tumor immunity and tumor microenvironment (TME) along with the importance of precision medicine in LXR-targeted therapies has been discussed to emphasize the LXRs as potent targets for the development of novel cancer therapeutics.
摘要:
癌症已成为严重的健康负担,导致每年的高发病率和高死亡率,主要是由于细胞内的各种分子改变。肝脏X受体(LXRs)失调是其中之一,在胆固醇代谢中起着至关重要的作用,脂类代谢和炎症在各种疾病如肥胖中也起着至关重要的作用,代谢功能障碍相关脂肪性肝病(MAFLD),心血管疾病,2型糖尿病,骨质疏松,和癌症。研究报告,LXRs的激活通过抑制细胞增殖来抑制癌症的生长,诱导细胞凋亡和自噬,调节胆固醇代谢,各种信号通路,如Wnt,和PI3K/AKT,调节细胞周期调节剂的表达水平,促进肿瘤微环境内的抗肿瘤免疫。在这次审查中,我们已经讨论了这个角色,结构,和LXRs的功能,并总结了它们的配体及其作用机理。此外,LXR在各种癌症中的作用,已经讨论了肿瘤免疫和肿瘤微环境(TME)以及精准医学在LXR靶向治疗中的重要性,以强调LXR是开发新癌症疗法的有效靶标。