Department of Transfusion, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Shangcheng District, Hangzhou, Zhejiang 310009, China.
J Biochem. 2024 Sep 30;176(4):313-324. doi: 10.1093/jb/mvae052.
Prostate cancer (PCa) has become a worldwide health burden among men. Previous studies have suggested that cellular retinoic acid binding protein 2 (CRABP2) significantly affects the regulation of cell proliferation, motility and apoptosis in multiple cancers; however, the effect of CRABP2 on PCa is poorly reported. CRABP2 expression in different PCa cell lines and its effect on different cellular functions varied. While CRABP2 promotes cell migration and invasion, it appears to inhibit cell proliferation specifically in PC-3 cells. However, the proliferation of DU145 and 22RV1 cells did not appear to be significantly affected by CRABP2. Additionally, CRABP2 had no influence on the cell cycle distribution of PCa cells. The RNA-seq assay showed that overexpressing CRABP2 upregulated laminin subunit beta-3 (LAMB3) mRNA expression, and the enrichment analyses revealed that the differentially expressed genes were enriched in the phosphoinositide 3-kinase (PI3K)/activated protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signalling pathways. The following western blot experiments also confirmed the upregulated LAMB3 protein level and the activation of the PI3K/AKT and MAPK signalling pathways. Moreover, overexpressing CRABP2 significantly inhibited tumour growth in vivo. In conclusion, CRABP2 facilitates cell migration and invasion by activating PI3K/AKT and MAPK signalling pathways through upregulating LAMB3 in PCa.
前列腺癌（PCa）已成为全球男性健康的负担。先前的研究表明，细胞视黄醇结合蛋白 2（CRABP2）显著影响多种癌症中细胞增殖、运动和凋亡的调节；然而，CRABP2 对 PCa 的影响报道甚少。CRABP2 在不同的 PCa 细胞系中的表达及其对不同细胞功能的影响各不相同。虽然 CRABP2 促进细胞迁移和侵袭，但它似乎特异性地抑制 PC-3 细胞的增殖。然而，DU145 和 22RV1 细胞的增殖似乎不受 CRABP2 的显著影响。此外，CRABP2 对 PCa 细胞的细胞周期分布没有影响。RNA-seq 分析表明，过表达 CRABP2 上调了层粘连蛋白亚基β-3（LAMB3）mRNA 的表达，富集分析显示差异表达基因富集在磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）和丝裂原活化蛋白激酶（MAPK）信号通路中。随后的 Western blot 实验也证实了 LAMB3 蛋白水平的上调和 PI3K/AKT 和 MAPK 信号通路的激活。此外，过表达 CRABP2 显著抑制了体内肿瘤的生长。总之，CRABP2 通过上调 PCa 中的 LAMB3 来激活 PI3K/AKT 和 MAPK 信号通路，促进细胞迁移和侵袭。
