Fu Lin, Dong Qianze, Xie Chengyao, Wang Yan, Li Qingchang
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 11000, Liaoning, China.
Tumour Biol. 2015 Feb;36(2):1015-22. doi: 10.1007/s13277-014-2706-2. Epub 2014 Oct 16.
CRKL is an adapter protein which is overexpressed in many malignant tumors and plays crucial roles in tumor progression. However, expression pattern and biological roles of CRKL in pancreatic cancer have not been examined. In the present study, we found that CRKL expression in pancreatic cancer specimens was higher than that in normal pancreatic tissues. Colony formation assay and Matrigel invasion assay showed that the overexpression of CRKL in Bxpc3 and Capan2 cell lines with low endogenous expression increased cell proliferation and invasion. Flow cytometry showed that CRKL promoted cell proliferation by facilitating cell cycle. Further analysis of cell cycle- and invasion-related molecules showed that CRKL upregulated cyclin D1, cyclin A, matrix metalloproteinase 2 (MMP2) expression, and phosphorylated extracellular signal (ERK)-regulated kinase. In conclusion, our study demonstrated that CRKL was overexpressed in human pancreatic cancers and contributed to pancreatic cancer cell proliferation and invasion through ERK signaling.
CRKL是一种衔接蛋白，在许多恶性肿瘤中过表达，并在肿瘤进展中发挥关键作用。然而，CRKL在胰腺癌中的表达模式和生物学作用尚未得到研究。在本研究中，我们发现胰腺癌标本中CRKL的表达高于正常胰腺组织。集落形成试验和基质胶侵袭试验表明，在低内源性表达的Bxpc3和Capan2细胞系中过表达CRKL可增加细胞增殖和侵袭。流式细胞术显示，CRKL通过促进细胞周期来促进细胞增殖。对细胞周期和侵袭相关分子的进一步分析表明，CRKL上调细胞周期蛋白D1、细胞周期蛋白A、基质金属蛋白酶2（MMP2）的表达，并使细胞外信号调节激酶（ERK）磷酸化。总之，我们的研究表明CRKL在人类胰腺癌中过表达，并通过ERK信号通路促进胰腺癌细胞的增殖和侵袭。
