Department of Immunology and Cell Biology, Laboratory of Intestinal Physiopathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.
Biomol Biomed. 2024 Sep 6;24(5):1117-1132. doi: 10.17305/bb.2024.10323.
The 67 kDa laminin receptor (67LR) was identified as the first laminin receptor shown to be involved in the carcinogenesis of various cancers, including colorectal cancer. While the exact composition of this 67 kDa receptor remains unknown, it has been reported to be formed by the 37 kDa ribosomal protein SA (RPSA) covalently attached to another unidentified protein. The goal of this study was to clarify the molecular structure of 67LR to enhance our understanding of its role in malignancies. Using cell fractionation of colorectal cancer cells, the 67 kDa immunoreactive protein corresponding to 67LR was found in the soluble protein fraction, while some of the 37 kDa RPSA exhibited plasma membrane-like properties. Proteomic analysis of the 67 kDa fraction revealed the absence of RPSA but identified the β-galactosidase-related 67 kDa elastin-binding protein (67EBP), another laminin binding receptor which presents amino acid sequence similarities that can explain the immune cross reactivity with RPSA. The downregulation of β-galactosidase through short hairpin RNA (shRNA) led to a reduction in both 67LR and 67EBP immunoreactive proteins, confirming the misidentification of 67LR and 67EBP in colorectal cancer cells. Based on these findings, we propose to redefine the 67LR as the RPSA-containing laminin receptor (RCLR) to avoid confusion with the 67EBP.
67 千道尔顿层粘连蛋白受体（67LR）被鉴定为第一个被证明参与各种癌症（包括结直肠癌）发生的层粘连蛋白受体。虽然这种 67 kDa 受体的确切组成尚不清楚，但据报道它是由 37 kDa 核糖体蛋白 SA（RPSA）共价连接到另一个未鉴定的蛋白质形成的。本研究的目的是阐明 67LR 的分子结构，以增强我们对其在恶性肿瘤中作用的理解。通过对结直肠癌细胞的细胞分级，发现与 67LR 相对应的 67 kDa 免疫反应性蛋白存在于可溶性蛋白部分，而一些 37 kDa RPSA 表现出类似质膜的特性。对 67 kDa 部分的蛋白质组学分析表明 RPSA 不存在，但鉴定了β-半乳糖苷酶相关的 67 kDa 弹性蛋白结合蛋白（67EBP），这是另一种层粘连蛋白结合受体，其氨基酸序列相似性可以解释与 RPSA 的免疫交叉反应性。通过短发夹 RNA（shRNA）下调β-半乳糖苷酶导致 67LR 和 67EBP 免疫反应性蛋白的减少，证实了结直肠癌细胞中 67LR 和 67EBP 的错误鉴定。基于这些发现，我们建议将 67LR 重新定义为含有 RPSA 的层粘连蛋白受体（RCLR），以避免与 67EBP 混淆。
