Increased Expression of Paxillin is Found in Human Oesophageal Squamous Cell Carcinoma: A Tissue Microarray Study

Li, BZ; W, Lei; Cy, Zhang; Zhou, Fang; N, Li; Ss, Shi; Xl, Feng; Zl, Chen; Hang, Jie; B, Qiu; Jt, Wan; Shao, Kwang‐Tsao; Xz, Xing; Xg, Tan; Wang, Z; Mh, Xiong

doi:10.1177/147323000803600209

Cited by 13 publications

(16 citation statements)

References 10 publications

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“…And this is also true in the context of ESCCs, as a number of the identified differentially expressed genes involved in integrin signaling in this study (listed in Supplementary Table S4) have already been previously implicated in ESCC pathogenesis. These include CAV1, ROCK1, ITGB1, ICAM1, VCL, PXN, and SHC1 (36)(37)(38)(39)(40)(41)(42)(43)(44). Here, we report the identification and characterization of a tumor suppressor gene Rab25 in ESCCs, which was found to be significantly downregulated in the integrin signaling-associated pathway.…”

Section: Discussionmentioning

confidence: 91%

Rab25 Is a Tumor Suppressor Gene with Antiangiogenic and Anti-Invasive Activities in Esophageal Squamous Cell Carcinoma

et al. 2012

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Esophageal squamous cell carcinoma (ESCC), the major histologic subtype of esophageal cancer, is a devastating disease characterized by distinctly high incidences and mortality rates. However, there remains limited understanding of molecular events leading to development and progression of the disease, which are of paramount importance to defining biomarkers for diagnosis, prognosis, and personalized treatment. By high-throughout transcriptome sequence profiling of nontumor and ESCC clinical samples, we identified a subset of significantly differentially expressed genes involved in integrin signaling. The Rab25 gene implicated in endocytic recycling of integrins was the only gene in this group significantly downregulated, and its downregulation was confirmed as a frequent event in a second larger cohort of ESCC tumor specimens by quantitative real-time PCR and immunohistochemical analyses. Reduced expression of Rab25 correlated with decreased overall survival and was also documented in ESCC cell lines compared with pooled normal tissues. Demethylation treatment and bisulfite genomic sequencing analyses revealed that downregulation of Rab25 expression in both ESCC cell lines and clinical samples was associated with promoter hypermethylation. Functional studies using lentiviral-based overexpression and suppression systems lent direct support of Rab25 to function as an important tumor suppressor with both anti-invasive and -angiogenic abilities, through a deregulated FAK-Raf-MEK1/2-ERK signaling pathway. Further characterization of Rab25 may provide a prognostic biomarker for ESCC outcome prediction and a novel therapeutic target in ESCC treatment. Cancer Res; 72(22); 6024-35. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 91%

Rab25 Is a Tumor Suppressor Gene with Antiangiogenic and Anti-Invasive Activities in Esophageal Squamous Cell Carcinoma

et al. 2012

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“…The combined detection of FAK and paxillin may have more value in detecting tumor cells. Li et al (13) reported that in 100 samples of esophageal carcinoma, 27 exhibited high paxillin gene expression but only 6 samples of adjacent atypical hyperplasia exhibited paxillin expression. In addition, Chatzizacharias et al found that 54/91 cases of esophageal carcinoma had FAK overexpression, and its positive rate of expression was 59.3%.…”

Section: Discussionmentioning

confidence: 99%

Expression of paxillin and FAK mRNA and the related clinical significance in esophageal carcinoma

et al. 2011

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Abstract. The objective of the present study was to investigate the expression of paxillin and focal adhesion kinase (FAK) mRNA in esophageal carcinoma tissues, and their relationship with clinicopathological parameters, as well as to analyze the correlation of paxillin and FAK mRNA levels in esophageal carcinoma. By using reverse transcription polymerase chain reaction (RT-PCR), the mRNA expression levels of paxillin and FAK were detected in 121 samples of esophageal carcinoma, 43 samples of atypical hyperplasia and 56 samples of normal esophageal mucosa. The results showed that the positive rates of paxillin and FAK mRNA expression in esophageal carcinoma were 87.6 and 80.17%, respectively, which were significantly higher (P<0.05) than those in atypical hyperplasia (44.19 and 39.53%) and normal esophageal mucosa (5.36 and 12.5%). Notably, paxillin and FAK mRNA expression levels were significantly correlated with the differentiation degree and depth of invasion of esophageal carcinoma and with lymph node metastasis (P<0.05). In addition, paxillin and FAK mRNA expression levels in esophageal carcinoma were positively correlated (r=0.4804, P=0.000).In conclusion, the combined detection of paxillin and FAK mRNA expression is expected to provide a theoretical basis for the molecular diagnosis of esophageal carcinoma. IntroductionPaxillin is a tyrosine kinase substrate and a significant cell adhesion molecule. Paxillin is associated with integrin and its related cellular and extracellular matrix molecules. As such, paxillin helps to regulate cell migration, dissemination and other functions, and enhances tumor cell invasion and metastasis (1,2). Focal adhesion kinase (FAK) is distributed in the cellular focal adhesion sites and plays a crucial role in the regulation of tumor cell migration (3,4). Thus, paxillin and FAK are both related to the occurrence of tumors and their biological behavior. In this study, reverse transcription polymerase chain reaction (RT-PCR) was used to detect paxillin and FAK mRNA expression in esophageal carcinoma, atypical dysplasia and normal esophageal mucosa. This study also investigated the relationship of paxillin, FAK and clinicopathological parameters, as well as the correlation between paxillin and FAK expression, in order to provide a theoretical basis for a molecular diagnostic for esophageal carcinoma. Materials and methodsGeneral information. Fresh specimens were collected from esophagectomies of 121 patients while visiting the Department of Oncology, Affiliated Hospital, Xuzhou Medical College (Jiangsu Province, China) from March 1, 2010 to March 1, 2011. Subjects included 68 males and 53 females, aged 35 to 80 years; all had no preoperative chemotherapy, radiotherapy or immunotherapy history. Shortly following specimen harvest, two samples were taken from each of three sites -necrosis-free carcinoma (within 3 cm of the expected carcinoma) and distant, normal mucosa. For each tissue, one of the two samples was stored in liquid nitrogen for later RT-PCR preparation. The second s...

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“…It provides a platform for the integration and processing of adhesion and growth factor-related signals that are mainly involved in tumor metastasis and cell proliferation [32], [33]. Paxillin is overexpressed in many carcinomas, including bladder cancer [33], ESCC [34], [35], hepatocellular carcinoma (HCC) [36], NSCLC [37], salivary adenoid cystic carcinoma [38], and floor of mouth carcinoma [39].…”

Section: Introductionmentioning

confidence: 99%

Fascin-1, Ezrin and Paxillin Contribute to the Malignant Progression and Are Predictors of Clinical Prognosis in Laryngeal Squamous Cell Carcinoma

et al. 2012

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AimsFascin-1, ezrin and paxillin, cytoskeleton-associated proteins, have been implicated in several human cancers, but their role in laryngeal squamous cell carcinoma (LSCC) is unknown. We investigated the association of their expression and clinicopathologic factors and their prognostic value in LSCC.Materials and MethodsQuantitative RT-PCR and western blot analyses were used to examine mRNA and protein levels in 10 fresh LSCC specimens and 10 corresponding adjacent normal margin (ANM) tissues from patients undergoing surgery in 2012. We used immunohistochemistry to retrospectively study 216 paraffin blocks of LSCC samples from patients (193 men) who had undergone surgery between 2000 and 2006 and had not received special treatment before the diagnosis. Univariate analysis of patient survival involved the Kaplan–Meier method. Multivariate analyses involved the Cox proportional hazards model.ResultsThe relative mRNA and protein levels of fascin-1, ezrin and paxillin were significantly greater in LSCC than ANM tissue (P<0.05). The high expression of fascin-1, ezrin or paxillin was positively correlated with poor tumor differentiation, cervical lymph node metastasis (N+), and advanced clinical stage (III+IV) (P<0.05) but not sex or metastasis. In addition, a high expression of fascin-1 (P = 0.007) or ezrin (P = 0.047) was associated with advanced tumor stage (T3+T4). The expression of fascin-1 was higher in smokers than non-smokers (P = 0.019). A high expression of fascin-1, ezrin or paxillin was associated with poor prognosis.ConclusionsFascin-1, ezrin and paxillin may be prognostic of poor outcome with LSCC after surgery. Our study may lead to establishing new molecular therapeutic targets and/or prognostic biomarkers in LSCC.

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Increased Expression of Paxillin is Found in Human Oesophageal Squamous Cell Carcinoma: A Tissue Microarray Study

Cited by 13 publications

References 10 publications

Rab25 Is a Tumor Suppressor Gene with Antiangiogenic and Anti-Invasive Activities in Esophageal Squamous Cell Carcinoma

Rab25 Is a Tumor Suppressor Gene with Antiangiogenic and Anti-Invasive Activities in Esophageal Squamous Cell Carcinoma

Expression of paxillin and FAK mRNA and the related clinical significance in esophageal carcinoma

Fascin-1, Ezrin and Paxillin Contribute to the Malignant Progression and Are Predictors of Clinical Prognosis in Laryngeal Squamous Cell Carcinoma

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