Roslan Zulaika, Muhamad Mudiana, Selvaratnam Lakshmi, Ab-Rahim Sharaniza
Institute of Medical and Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.
Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.
J Oncol. 2019 Mar 26;2019:4536302. doi: 10.1155/2019/4536302. eCollection 2019.
Low-density lipoprotein receptor (LDLR) has been an object of research since the 1970s because of its role in various cell functions. The LDLR family members include LRP5, LRP6, and LRP8. Even though LRP5, 6, and 8 are in the same family, intriguingly, these three proteins have various roles in physiological events, as well as in regulating different mechanisms in various kinds of cancers. LRP5, LRP6, and LRP8 have been shown to play important roles in a broad panel of cancers. LRP5 is highly expressed in many tissues and is involved in the modulation of glucose-induced insulin secretion, bone development, and cholesterol metabolism, as well as cancer progression. Recently, LRP5 has also been shown to play a role in chondroblastic subtype of osteosarcoma (OS) and prostate cancer and also in noncancer case such as osteoporosis. LRP6, which has been previously discovered to share the same structures as LRP5, has also been associated with many cancer progressions such as human triple negative breast cancer (TNBC), primary chronic lymphocytic leukemia (CLL), nonsmall cell lung cancer (NSCL), lung squamous cell carcinoma (LSCC), and hepatocellular carcinoma (HCC). In addition to its role in cancer progression, LRP8 (apolipoprotein E receptor 2 [APOER2]) has also been demonstrated to regulate canonical Wnt/-catenin signaling pathway whereby this pathway plays a role in cell migration and development. Therefore, this review aimed to elucidate the role of LRP 5, 6, and 8 in regulating the cancer progression.
自20世纪70年代以来，低密度脂蛋白受体（LDLR）因其在多种细胞功能中的作用而成为研究对象。LDLR家族成员包括LRP5、LRP6和LRP8。尽管LRP5、6和8属于同一家族，但有趣的是，这三种蛋白质在生理事件以及调节各种癌症的不同机制中具有多种作用。LRP5、LRP6和LRP8已被证明在多种癌症中发挥重要作用。LRP5在许多组织中高度表达，参与调节葡萄糖诱导的胰岛素分泌、骨骼发育、胆固醇代谢以及癌症进展。最近，LRP5还被证明在骨肉瘤（OS）的成软骨细胞亚型和前列腺癌以及骨质疏松症等非癌症病例中发挥作用。LRP6先前被发现与LRP5具有相同的结构，也与许多癌症进展相关，如人类三阴性乳腺癌（TNBC）、原发性慢性淋巴细胞白血病（CLL）、非小细胞肺癌（NSCL）、肺鳞状细胞癌（LSCC）和肝细胞癌（HCC）。除了在癌症进展中的作用外，LRP8（载脂蛋白E受体2 [APOER2]）还被证明可调节经典的Wnt/β-连环蛋白信号通路，该通路在细胞迁移和发育中发挥作用。因此，本综述旨在阐明LRP 5、6和8在调节癌症进展中的作用。
