Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer

Journal of Translational Medicine, Nov 2013

Background Paxillin (PXN) has been found to be aberrantly regulated in various malignancies and involved in tumor growth and invasion. The clinicopathological and prognostic significance of PXN in gastric cancer is still unclear. Methods The expression of PXN was determined in paired gastric cancer tissues and adjacent normal tissues by Western blotting and real-time PCR. Immunohistochemistry was performed to detect the expression of PXN in 239 gastric cancer patients. Statistical analysis was applied to investigate the correlation between PXN expression and clinicopathological characteristics and prognosis in patients. Additionally, the effects of PXN on gastric cancer cell proliferation and migration were also evaluated. Results PXN was up-regulated in gastric cancer tissues and cell lines as compared with adjacent normal tissues and normal gastric epithelial cell line GES-1. Overexpression of PXN was correlated with distant metastasis (P = 0.001) and advanced tumor stage (P = 0.021) in gastric cancer patients. Patients with high PXN expression tended to have poor prognosis compared with patients with low PXN expression (P < 0.001). Multivariate analysis demonstrated that PXN expression was an independent prognostic factor (P = 0.020). Moreover, ectopic expression of PXN promotes cell proliferation and migration in AGS cells whereas knockdown of PXN inhibits cell proliferation and migration in SGC7901 cells. Conclusions PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer.

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Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer

Dong-liang Chen 0 1 Zhi-qiang Wang 0 1 Chao Ren 0 1 Zhao-lei Zeng 1 De-shen Wang 0 1 Hui-yan Luo 0 1 Feng Wang 0 1 Miao-zhen Qiu 0 1 Long Bai 0 1 Dong-sheng Zhang 0 1 Feng-hua Wang 0 1 Yu-hong Li 0 1 Rui-hua Xu 0 1 0 Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Dong Feng East Road, 510060 Guangzhou , P.R. China 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Dong Feng East Road, 510060 Guangzhou , P.R. China Background: Paxillin (PXN) has been found to be aberrantly regulated in various malignancies and involved in tumor growth and invasion. The clinicopathological and prognostic significance of PXN in gastric cancer is still unclear. Methods: The expression of PXN was determined in paired gastric cancer tissues and adjacent normal tissues by Western blotting and real-time PCR. Immunohistochemistry was performed to detect the expression of PXN in 239 gastric cancer patients. Statistical analysis was applied to investigate the correlation between PXN expression and clinicopathological characteristics and prognosis in patients. Additionally, the effects of PXN on gastric cancer cell proliferation and migration were also evaluated. Results: PXN was up-regulated in gastric cancer tissues and cell lines as compared with adjacent normal tissues and normal gastric epithelial cell line GES-1. Overexpression of PXN was correlated with distant metastasis (P = 0.001) and advanced tumor stage (P = 0.021) in gastric cancer patients. Patients with high PXN expression tended to have poor prognosis compared with patients with low PXN expression (P < 0.001). Multivariate analysis demonstrated that PXN expression was an independent prognostic factor (P = 0.020). Moreover, ectopic expression of PXN promotes cell proliferation and migration in AGS cells whereas knockdown of PXN inhibits cell proliferation and migration in SGC7901 cells. Conclusions: PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer. - Background Gastric cancer is among the most frequently diagnosed cancer and the second leading cause of cancer-related mortality worldwide [1,2]. In spite of recent improvement in the clinical treatment of gastric cancer, patients with advanced stage of gastric cancer still have poor survival. Surgical resection is still the only curative therapy available for this disease [3]. Under this circumstance, there is an urgent need to better understand the biological mechanism of this neoplasm so as to guide patient management and develop novel therapeutic strategies. The paxillin (PXN) gene was first identified as a tyrosine-containing protein in cells transformed by the src oncogene [4] and encodes for a focal adhesion molecule of 68 kD [5]. PXN functions as an adaptor protein that coordinates multiple signals from integrins, growth factors and cell surface receptors [6]. By these proteinprotein interactions, PXN regulates diverse physiological process, such as gene expression, matrix organization, tissue remolding, cell proliferation and survival, cell motility and metastasis [6-8]. In addition to the interactions with cytoskeleton proteins, PXN could also bind to several oncogenic proteins, such as v-Src, E6 and BCR-ABL [9-13]. Such proteins could use PXN as a docking site or as a substrate to interrupt or mislead the normal adhesion and growth factor signaling pathways that are essential for controlled cellular growth and migration [5]. PXN has been found to be involved in many tumor types. A previous study reported that PXN could inhibit lung cancer proliferation and motility [14]. However, more recent studies found PXN was overexpressed and acted as an pro-oncogene in a variety of tumors, including non-small cell lung cancer, colorectal cancer, prostate cancer and cervical carcinoma [15-20]. In gastric cancer, Li et al. reported that PXN (tyr118) phosphorylation was a key factor for fibronectin-stimulated invasiveness of AGS cells [21]. However, the clinicopathological and prognostic role of PXN in gastric cancer is still unclear. In this study, we detected the PXN mRNA and protein level in 30 paired tumor tissues and adjacent normal tissues and found that PXN was frequently up-regulated in tumor tissues. In addition, the expression of PXN was associated with poor prognosis in a large cohort of 239 patients. Furthermore, ectopic expression/knockdown of PXN could promote/inhibit cell proliferation and migration in gastric cancer cells. Materials and methods Human tissue specimens and cell lines This study was approved by the ethics committee of Sun Yat -sen University Cancer Center and written informed consents for using the samples for research purpose were obtained from all the patients before surgery. We collected 239 paraffin-embedded, archived tissue samples from patients who underwent surgery in Sun Yat-sen University Cancer Center (Gu (...truncated)


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Dong-liang Chen, Zhi-qiang Wang, Chao Ren, Zhao-lei Zeng, De-shen Wang, Hui-yan Luo, Feng Wang, Miao-zhen Qiu, Long Bai, Dong-sheng Zhang, Feng-hua Wang, Yu-hong Li, Rui-hua Xu. Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer, Journal of Translational Medicine, 2013, pp. 277, 11, DOI: 10.1186/1479-5876-11-277