Dataset Information

AXL is a marker for epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a common cancer in China and certain other parts of the world with a dismal prognosis for affected patients. AXL is a member of the TYRO3-AXL-MER family of receptor tyrosine kinases, and has been revealed to be an important mediator of epithelial-mesenchymal transition (EMT) in several types of cancer. However, to the best of our knowledge, its function in EMT in ESCC cells has not yet been examined. The present study employed two independent ESCC mRNA profile datasets and revealed that AXL is associated with several EMT markers. Gene Set Enrichment Analysis indicated that EMT occurs more in ESCC with high AXL expression. Analysis on another dataset demonstrated further that increased expression of AXL in ESCC is associated with increased migratory ability. Collectively, the results of the present study provide evidence that AXL is a marker for EMT in ESCC.

SUBMITTER: Zhang G

PROVIDER: S-EPMC5774429 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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AXL is a marker for epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

Zhang Guoan G Kong Xia X Wang Meng M Zhao Hongli H Han Sha S Hu Ronghang R Huang Jian J Cui Wen W

Oncology letters 20171120 2

Esophageal squamous cell carcinoma (ESCC) is a common cancer in China and certain other parts of the world with a dismal prognosis for affected patients. AXL is a member of the TYRO3-AXL-MER family of receptor tyrosine kinases, and has been revealed to be an important mediator of epithelial-mesenchymal transition (EMT) in several types of cancer. However, to the best of our knowledge, its function in EMT in ESCC cells has not yet been examined. The present study employed two independent ESCC mRN ...[more]

PMID: 29434888

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Project description:BACKGROUND:We attempted to identify novel biomarkers and therapeutic targets for esophageal squamous cell carcinoma by gene expression profiling of frozen esophageal squamous carcinoma specimens and examined the functional relevance of a newly discovered marker gene, WDR66. METHODS:Laser capture microdissection technique was applied to collect the cells from well-defined tumor areas in collaboration with an experienced pathologist. Whole human gene expression profiling of frozen esophageal squamous carcinoma specimens (n = 10) and normal esophageal squamous tissue (n = 18) was performed using microarray technology. A gene encoding WDR66, WD repeat-containing protein 66 was significantly highly expressed in esophageal squamous carcinoma specimens. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort (n = 71) consisting of esophageal squamous cell carcinoma (n = 25), normal esophagus (n = 11), esophageal adenocarcinoma (n = 13), gastric adenocarcinoma (n = 15) and colorectal cancers (n = 7). In order to understand WDR66's functional relevance siRNA-mediated knockdown was performed in a human esophageal squamous cell carcinoma cell line, KYSE520 and the effects of this treatment were then checked by another microarray analysis. RESULTS:High WDR66 expression was significantly associated with poor overall survival (P = 0.031) of patients suffering from esophageal squamous carcinomas. Multivariate Cox regression analysis revealed that WDR66 expression remained an independent prognostic factor (P = 0.042). WDR66 knockdown by RNA interference resulted particularly in changes of the expression of membrane components. Expression of vimentin was down regulated in WDR66 knockdown cells while that of the tight junction protein occludin was markedly up regulated. Furthermore, siRNA-mediated knockdown of WDR66 resulted in suppression of cell growth and reduced cell motility. CONCLUSIONS:WDR66 might be a useful biomarker for risk stratification of esophageal squamous carcinomas. WDR66 expression is likely to play an important role in esophageal squamous cell carcinoma growth and invasion as a positive modulator of epithelial-mesenchymal transition. Furthermore, due to its high expression and possible functional relevance, WDR66 might be a novel drug target for the treatment of squamous carcinoma.

Project description:BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Due to its high morbidity and mortality rates, it is urgent to find a molecular target that contributes to esophageal carcinogenesis and progression. In this research, we aimed to investigate the functions of Latent transforming growth factor ? binding protein 1(LTBP1) in ESCC progression and elucidate the underlying mechanisms. METHODS:The tandem mass tag-based quantitative proteomic approach was applied to screen the differentially expressed proteins (DEPs) between 3 cases of ESCC tumor samples and paired normal tissues. Then the DEPs were validated in human ESCC tissues using western blot assays and GEPIA database respectively. The expression level of LTBP1 was detected in 152 cases of ESCC tissues and paired normal tissues. Loss-of-function assays were performed to detect the function of LTBP1 in vivo and in vitro. Immunofluorescence and Western blot assays were used to detect the expression of apoptosis, epithelial-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) markers. RESULTS:A total of 39 proteins were screened to be up-regulated (ratio?>?2.0) in all three ESCC tissues. The results of immunohistochemistry assays indicated that the expression level of LTBP1 was higher in ESCC tissues than that in paired normal tissues (p?<?0.001). Overexpression of LTBP1 was positively associated with lymphatic metastasis in ESCC (p?=?0.002). Down-regulation of LTBP1 inhibited the invasion and migration as well as metastatic abilities in vitro and in vivo. It was also observed the down-regulation of LTBP1 not only decreased the mesenchymal phenotypes but also inhibited TGF?-induced EMT in ESCC cells. We further found that down-regulation of LTBP1 enhanced ESCC cells' sensitivity to 5-FU treatment. Inhibition of LTBP1 expression could also attenuate induction of CAFs transformation and restrain fibroblast express fibronectin (FN1) in ESCC cells. CONCLUSION:Overexpression of LTBP1 was associated with lymph node metastasis in ESCC. Our results indicated that LTBP1 not only increased the malignant behaviors of ESCC cells but also induced EMT and CAFs transformation. Our studies suggested an oncogenic role of LTBP1 in ESCC progression and it may serve as a potential therapeutic target for ESCC patients.

Dataset Information

AXL is a marker for epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

Publications

AXL is a marker for epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

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