Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer
Dong-liang Chen
0
1
Zhi-qiang Wang
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1
Chao Ren
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1
Zhao-lei Zeng
1
De-shen Wang
0
1
Hui-yan Luo
0
1
Feng Wang
0
1
Miao-zhen Qiu
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1
Long Bai
0
1
Dong-sheng Zhang
0
1
Feng-hua Wang
0
1
Yu-hong Li
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1
Rui-hua Xu
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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.
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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)