Department of Hematology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People's Republic of China.
Laboratory of Clinical Molecular Cytogenetics and Immunology, The First Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China.
Med Oncol. 2024 Jun 19;41(7):180. doi: 10.1007/s12032-024-02399-1.
Low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6), a member of the LDLR superfamily of cell surface receptors, is most widely known as a crucial co-receptor in the activation of canonical Wnt/β-catenin signaling. This signaling pathway is implicated in multiple biological processes, such as lipoprotein metabolism, protease regulation, cell differentiation, and migration. LRP6 is frequently overexpressed in a variety of tumors, including liver cancer, colorectal cancer, and prostate cancer, and is generally considered an oncogene that promotes tumor proliferation, migration, and invasion. However, there are exceptions; some studies have reported that LRP6 inhibits lung metastasis of breast cancer through its ectodomain (LRP6N), and patients with low LRP6 expression tend to have a poor prognosis. Thus, the role of LRP6 in tumors remains controversial. Although limited studies have shown that LRP6 is associated with the expression and roles of a variety of immune cells in tumors, the interaction of LRP6 with the tumor microenvironment (TME) is not fully understood. Furthermore, it is crucial to acknowledge that LRP6 can engage with alternative pathways, including the mTORC1, CXCL12/CXCR4, and KRAS signaling pathways mentioned earlier, resulting in the regulation of biological functions independent of canonical Wnt/β-catenin signaling. Due to the potential of LRP6 as a molecular target for cancer therapy, various treatment modalities have been developed to directly or indirectly inhibit LRP6 function, demonstrating promising anti-cancer effects across multiple cancer types. This review will concentrate on exploring the expression, function, and potential therapeutic applications of LRP6 in different cancer types, along with its influence on the TME.
低密度脂蛋白受体 (LDLR) 相关蛋白 6 (LRP6)，是 LDLR 家族细胞表面受体的成员，作为经典 Wnt/β-连环蛋白信号通路激活的关键共受体而广为人知。该信号通路参与多种生物学过程，如脂蛋白代谢、蛋白酶调节、细胞分化和迁移。LRP6 在多种肿瘤中广泛过表达，包括肝癌、结直肠癌和前列腺癌，通常被认为是促进肿瘤增殖、迁移和侵袭的致癌基因。然而，也有例外；一些研究报道 LRP6 通过其外显子（LRP6N）抑制乳腺癌的肺转移，而 LRP6 表达水平低的患者往往预后不良。因此，LRP6 在肿瘤中的作用仍存在争议。尽管有限的研究表明 LRP6 与肿瘤中多种免疫细胞的表达和功能有关，但 LRP6 与肿瘤微环境 (TME) 的相互作用尚未完全阐明。此外，必须认识到 LRP6 可以与替代途径相互作用，包括前文提到的 mTORC1、CXCL12/CXCR4 和 KRAS 信号通路，从而调节独立于经典 Wnt/β-连环蛋白信号通路的生物学功能。由于 LRP6 作为癌症治疗的分子靶标具有潜力，因此已经开发了各种治疗方法来直接或间接地抑制 LRP6 功能，在多种癌症类型中表现出有前途的抗癌效果。本综述将重点探讨 LRP6 在不同癌症类型中的表达、功能和潜在治疗应用，以及其对 TME 的影响。
