Department of Translational Medical Sciences, University of Naples Federico II, Naples. Italy.
Department of Chemistry, University of Salerno, Salerno. Italy.
Curr Pharm Des. 2017;23(32):4745-4757. doi: 10.2174/1381612823666170710125332.
The 67 kDa high affinity laminin receptor (67LR) is a non-integrin cell surface receptor for laminin, the major component of basement membranes. Interactions between 67LR and laminin play a major role in mediating cell adhesion, migration, proliferation and survival. 67LR derives from homo- or hetero-dimerization of a 37 kDa cytosolic precursor (37LRP), most probably by fatty acid acylation. Interestingly, 37LRP, also called p40 or OFA/iLR (oncofetal antigen/immature laminin receptor), is a multifunctional protein with a dual activity in the cytoplasm and in the nucleus. In the cytoplasm, 37LRP it is associated with the 40S subunit of ribosome, playing a critical role in protein translation and ribosome biogenesis while in the nucleus it is tightly associated with nuclear structures, and bound to components of the cytoskeleton, such as tubulin and actin. 67LR is mainly localized in the cell membrane, concentrated in lipid rafts. Acting as a receptor for laminin is not the only function of 67LR; indeed, it also acts as a receptor for viruses, bacteria and prions. 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potential. The primary function of 67LR in cancer is to promote tumor cell adhesion to basement membranes, the first step in the invasion-metastasis cascade. Thus, 67LR is overexpressed in neoplastic cells as compared to their normal counterparts and its overexpression is considered a molecular marker of metastatic aggressiveness in cancer of many tissues, including breast, lung, ovary, prostate, stomach, thyroid and also in leukemia and lymphoma. Thus, inhibiting 67LR binding to laminin could be a feasible approach to block cancer progression. Here, we review the current understanding of the structure and function of this molecule, highlighting its role in cancer invasion and metastasis and reviewing the various therapeutic options targeting this receptor that could have a promising future application.
67 kDa 高亲和力层粘连蛋白受体（67LR）是层粘连蛋白的非整联蛋白细胞表面受体，层粘连蛋白是基底膜的主要成分。67LR 与层粘连蛋白的相互作用在介导细胞黏附、迁移、增殖和存活中起着重要作用。67LR 来源于 37 kDa 胞质前体（37LRP）的同源或异源二聚体，最有可能通过脂肪酸酰化。有趣的是，37LRP，也称为 p40 或 OFA/iLR（癌胚抗原/未成熟层粘连蛋白受体），是一种多功能蛋白，在细胞质和细胞核中具有双重活性。在细胞质中，37LRP 与核糖体的 40S 亚基结合，在蛋白质翻译和核糖体生物发生中发挥关键作用，而在细胞核中，它与核结构紧密结合，并与细胞骨架成分如微管蛋白和肌动蛋白结合。67LR 主要定位于细胞膜，集中在脂筏中。作为层粘连蛋白的受体并不是 67LR 的唯一功能；事实上，它还作为病毒、细菌和朊病毒的受体。67LR 的表达在肿瘤细胞中增加，并与增强的侵袭和转移潜能相关。67LR 在癌症中的主要功能是促进肿瘤细胞与基底膜的黏附，这是侵袭-转移级联的第一步。因此，与正常细胞相比，肿瘤细胞中 67LR 过度表达，其过度表达被认为是许多组织包括乳腺癌、肺癌、卵巢癌、前列腺癌、胃癌、甲状腺癌以及白血病和淋巴瘤的癌症转移侵袭性的分子标志物。因此，抑制 67LR 与层粘连蛋白的结合可能是阻止癌症进展的可行方法。在这里，我们综述了对这种分子的结构和功能的当前理解，强调了它在癌症侵袭和转移中的作用，并综述了针对这种受体的各种治疗选择，这些选择可能具有有前途的未来应用。
