Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, China.
Mol Carcinog. 2013 Nov;52(11):890-9. doi: 10.1002/mc.21935. Epub 2012 Jun 29.
Crk-Like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration. Amplification of CRKL gene was found in non-small cell lung cancer (NSCLC). However, the expression pattern of CRKL protein and its clinical significance in human NSCLC have not been well characterized to date. In this study, expression of CRKL was evaluated in 131 NSCLC tissues by immumohistochemistry. CRKL protein was up-regulated in the lung carcinomas compared with adjacent normal lung tissue. Overexpression of CRKL was found in 58 of 131 (44.3%) NSCLC samples and correlated with poor tumor differentiation (P = 0.0042), histological type (adenocarcinoma; P = 0.001), advanced p-TNM stage (P = 0.0004), nodal metastasis (P = 0.0273), high proliferation index (P = 0.0062) and poor overall survival (P = 0.0084). Further univariate and multivariate analysis showed a significant association of CRKL overexpression and worse overall survival in lung cancer patients. In addition, overexpression of CRKL in HBE and H1299 cell lines promoted cell proliferation by facilitating cell cycle progression. Further analysis of cell cycle related molecules showed that CRKL induced cyclin D1, cyclin B1 expression, and increased Rb phosphorylation. In conclusion, this study demonstrated overexpression of CRKL correlated with poor prognosis and lung cancer proliferation by cell cycle regulation.
Crk 样蛋白（CRKL）是一种衔接蛋白，在多种生物学过程中发挥着关键作用，包括细胞增殖、黏附和迁移。非小细胞肺癌（NSCLC）中发现 CRKL 基因扩增。然而，迄今为止，CRKL 蛋白在人类 NSCLC 中的表达模式及其临床意义尚未得到充分描述。在这项研究中，通过免疫组织化学评估了 131 例 NSCLC 组织中 CRKL 的表达。与相邻正常肺组织相比，肺癌中 CRKL 蛋白呈上调表达。在 131 例 NSCLC 样本中，发现 58 例（44.3%）存在 CRKL 过表达，且与肿瘤分化差（P=0.0042）、组织学类型（腺癌；P=0.001）、晚期 p-TNM 分期（P=0.0004）、淋巴结转移（P=0.0273）、高增殖指数（P=0.0062）和总生存不良（P=0.0084）相关。进一步的单因素和多因素分析显示，CRKL 过表达与肺癌患者总生存不良显著相关。此外，在 HBE 和 H1299 细胞系中过表达 CRKL 通过促进细胞周期进程促进细胞增殖。对细胞周期相关分子的进一步分析表明，CRKL 诱导 cyclin D1、cyclin B1 表达，并增加 Rb 磷酸化。总之，本研究表明，CRKL 过表达与不良预后和肺癌增殖有关，其机制与细胞周期调控有关。
