Overexpression of CRKL correlates with poor prognosis and cell proliferation in non-small cell lung cancer.

Abstract

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.

• Authors: Yan Wang, Qian-ze Dong, Ling Fu, Maggie Stoecker, Endi Wang, En-Hua Wang
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 52 Issue 11 Pg. 890-9 (Nov 2013) ISSN: 1098-2744 [Electronic] United States
• PMID: 22753141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Wiley Periodicals, Inc.

Chemical References

• Adaptor Proteins, Signal Transducing
• CRKL protein
• Nuclear Proteins
• Cyclin D1
• Cyclin-Dependent Kinase 6

Topics

• Adaptor Proteins, Signal Transducing (analysis, genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (diagnosis, genetics, metabolism, pathology)
• Cell Cycle
• Cell Line, Tumor
• Cell Proliferation
• Cyclin D1 (genetics, metabolism)
• Cyclin-Dependent Kinase 6 (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung (metabolism, pathology)
• Lung Neoplasms (diagnosis, genetics, metabolism, pathology)
• Male
• Middle Aged
• Nuclear Proteins (analysis, genetics, metabolism)
• Prognosis
• Up-Regulation