The Roles of Low-Density Lipoprotein Receptor-Related Proteins 5, 6, and 8 in Cancer: A Review

Abstract

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/β-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.

<p>The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer</p>

“…The low-density lipoprotein receptor‐related protein families are transmembrane proteins, limited to the regulation of cholesterol homeostasis by receptor‐mediated endocytosis of lipoprotein particles; however, there is growing experimental evidence that the other members of the gene family have additional physiological functions, including signal transduction 4. Members of the LRP family, including LDLR related protein 1 (LRP1), LRP2/glycoprotein330/megalin, very low-density lipoprotein (VLDL) receptor (VLDLR); LR11 (also known as sorLA); apolipoprotein E (apoE) receptor type 2 (apoER2, LRP8, LR7/8B); LRP3, MEGF7/LRP4, LRP5, and LRP6, LR32 (also called LRP1B), as well as the LRP11 5,6. Many studies have reported that family members LRP1 and LRP1B serve as prognostic markers in colon cancer, breast cancer, thyroid cancer, urothelial and clear-cell renal cell carcinoma that they play important roles in carcinogenesis 7–15.…”

Contribution of the Low-Density Lipoprotein Receptor Family to Breast Cancer Progression

“…More recently, some LRPs have been identified as direct molecular targets for BC. LRP6 is probably the most promising target in the TNBC with its overexpression leading to Wnt signaling pathway activation together with tumorigenesis promotion ( 5 ). Several drugs such as salinomycin, prodigiosin, and niclosamide indeed induce LRP6 phosphorylation and degradation leading to decreased tumor growth ( 49 , 50 , 95 ).…”

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

“…Lrp8 is located on chromosome 3 and has a length of 3291 bp, and it encodes a protein called low-density lipoprotein receptor-related protein 8. In recent years, Lrp8 has been revealed to play a role in cell development and migration via the regulation of the canonical Wnt/β-catenin signaling pathway [33]. Hence, Lrp8 is actively involved in the regulation of tumor and bone diseases [31,32].…”