Fibronectin Promotes Tyrosine Phosphorylation of Paxillin and Cell Invasiveness in the Gastric Cancer Cell Line AGS

Li, Dan; Ding, Jian; Wang, Xiaozhong; Wang, Chengdang; Wu, Ting

doi:10.1177/030089160909500621

Cited by 18 publications

(15 citation statements)

References 51 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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BackgroundPaxillin (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.MethodsThe 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.ResultsPXN 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.ConclusionsPXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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“…1). On a larger amount of adsorbed fibronectin, it has been documented that the turnover of focal adhesions is promoted with active cell migration through paxillin phosphorylation (23,24). Paxillin phosphorylation enhances the turnover of focal adhesion with lamellipodium protrusions, whereas non-phosphorylated paxillin leads to the formation of fibrillar adhesions (25).…”

Section: Discussionmentioning

confidence: 99%

Changes in human mesenchymal stem cell behaviors on dendrimer-immobilized surfaces due to mediation of fibronectin adsorption and assembly

Ogawa

Kim

Kino‐oka

2015

Journal of Bioscience and Bioengineering

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Dynamic changes of morphologies in human mesenchymal stem cells (hMSCs) were investigated on dendrimer surfaces with different capacities for fibronectin adsorption by changing the polymeric generation numbers of first (G1), third (G3), and fifth (G5) generations. The amount of adsorbed fibronectin on dendrimer surfaces increased with the generation number. Time-lapse observations revealed that cells on the G1 surface maintained their shape with formation of fibronectin fibrils in the bodies, introducing to the stabilization of focal adhesion with enriched stress fibers. Cells on the G3 surface showed partial contraction with degradation of fibril structures in the trailing edge. Cells on the G5 surface changed the shape by active extension and strong contracting without stabilization of focal adhesion through the formation of fibronectin aggregates and immature stress fibers. In addition, the paxillin which is a focal adhesion protein at lamellipodia was phosphorylated, leading to active lamellipodium protrusions. These results indicate that the amount and structure of fibronectin affects dynamic hMSC behaviors through the formation of cytoskeletons and focal adhesions.

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“…Li et al (23) documented that positive paxillin expression was significantly associated with low differentiation, with the presence of portal vein thrombosis, and with extra-hepatic metastasis of hepatocellular cell carcinoma. Li et al (24) found that paxillin positivity in human gastric cancer was associated with tumor stage, and siRNA targeting paxillin decreased the phosphorylation of paxillin (tyr118) and the invasiveness of AGS cells significantly as compared with controls. Previously, it was identified that overexpression of wild-type paxillin plasmids promoted cell proliferation and also enhanced migration, invasive capacity and metastasis of the colorectal cancer cells (25).…”

Section: Discussionmentioning

confidence: 99%

Paxillin expression is closely linked to the pathogenesis, progression and prognosis of gastric carcinomas

Xiao

Zhao

et al. 2013

Oncology Letters

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Paxillin encodes a focal adhesion-associated protein and is involved in the progression and aggressive phenotypes of malignancies through its interactions with the actin cytoskeleton and key signal transduction oncogenes. The present study aimed to investigate the clinicopathological and prognostic significance of paxillin in gastric cancer. The expression of paxillin was evaluated using tissue microarrays of gastric adjacent non-cancerous mucosa, adenoma and carcinoma specimens by immunohistochemistry. Paxillin expression was compared against clinicopathological parameters and the survival time of the patients. Paxillin was highly expressed in gastric adenoma compared with that in non-neoplastic mucosa and carcinoma (P<0.05). Paxillin expression was lower in the younger carcinoma patients compared with that in the elder carcinoma patients (P<0.05). Paxillin expression was negatively correlated with tumor size, depth of invasion and lymph node metastasis, but not with patient gender, lymphatic or venous invasion, or TNM staging (P>0.05). Higher paxillin expression was observed in intestinal-type compared with diffuse-type carcinoma (P<0.05). Kaplan-Meier analysis indicated a positive association between paxillin expression and cumulative survival rate in all, advanced and intestinal-type carcinoma patients (P<0.05). Multivariate analysis using the Cox proportional hazards model indicated that patient age, depth of invasion, lymphatic invasion, lymph node metastasis, TNM staging and Lauren classification were independent prognostic factors for all gastric carcinomas (P<0.05). Aberrant paxillin expression may be involved in the growth, invasion, metastasis and differentiation of gastric carcinoma. Altered paxillin expression may, therefore, be employed as an indicator of pathobiological behaviors and prognosis of gastric carcinomas.

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Fibronectin Promotes Tyrosine Phosphorylation of Paxillin and Cell Invasiveness in the Gastric Cancer Cell Line AGS

Abstract: Fibronectin promotes paxillin (tyr118) phosphorylation and invasiveness of AGS cells. Paxillin silencing by RNA interference inhibits the cell invasiveness stimulated by fibronectin. Paxillin is a key factor in the fibronectin-stimulated invasiveness of AGS cells.

Cited by 18 publications

References 51 publications

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

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

Changes in human mesenchymal stem cell behaviors on dendrimer-immobilized surfaces due to mediation of fibronectin adsorption and assembly

Paxillin expression is closely linked to the pathogenesis, progression and prognosis of gastric carcinomas

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