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

Authors

  • Yan Wang,

    Corresponding author
    1. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, China
    • Department of Pathology, The First Affiliated Hospital of China Medical University and Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.

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  • Qian-ze Dong,

    1. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, China
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  • Ling Fu,

    1. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, China
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  • Maggie Stoecker,

    1. Department of Pathology, Duke University Medical Center, Durham, North Carolina
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  • Endi Wang,

    1. Department of Pathology, Duke University Medical Center, Durham, North Carolina
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  • En-Hua Wang

    1. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, China
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  • No potential conflicts of interest were disclosed.

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. © 2012 Wiley Periodicals, Inc.

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