Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of General Surgery, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Apr 1;51(4):356-364. doi: 10.1093/abbs/gmz019.
Metastasis is the main cause of death in patients with colorectal cancer (CRC), but the molecular mechanism is not yet fully understood. Previous studies have shown that P zero-related protein (PZR), a member of the immunoglobulin family, can promote fibronectin-dependent migration of mouse embryonic fibroblasts as well as invasion and metastasis of hepatic carcinoma cells. However, the role of PZR in CRC remains unclear. In this study, we determined the ectopic expression of PZR in CRC tissues, and results showed that PZR expression was increased not only in tumors with higher pathological stage, but also in tumors with distant metastasis. Through PZR-knockdown and overexpression in CRC cell lines, we found that the expression of PZR had significant effect on the invasion and migration of CRC cells as well as the phosphorylation of pro-metastasis proteins including focal adhesion kinase (FAK) and Src. Taken together, this study indicates that PZR may promote the invasion and migration of CRC cells through increasing the phosphorylation of FAK and Src, which provides a new theoretical basis and a possible marker for the diagnosis or prognosis of CRC metastasis.
转移是结直肠癌（CRC）患者死亡的主要原因，但分子机制尚不完全清楚。先前的研究表明，P 零相关蛋白（PZR）是免疫球蛋白家族的成员，可促进小鼠胚胎成纤维细胞依赖纤维连接蛋白的迁移以及肝癌细胞的侵袭和转移。然而，PZR 在 CRC 中的作用尚不清楚。在这项研究中，我们确定了 PZR 在 CRC 组织中的异位表达，结果表明 PZR 表达不仅在高病理分期的肿瘤中增加，而且在远处转移的肿瘤中也增加。通过在 CRC 细胞系中敲低和过表达 PZR，我们发现 PZR 的表达对 CRC 细胞的侵袭和迁移以及包括粘着斑激酶（FAK）和Src 在内的促转移蛋白的磷酸化有显著影响。总之，这项研究表明，PZR 可能通过增加 FAK 和 Src 的磷酸化来促进 CRC 细胞的侵袭和迁移，为 CRC 转移的诊断或预后提供了新的理论依据和可能的标志物。
