Epithelial-mesenchymal Transition In Esophageal Cancer Research Articles

Dexmedetomidine hydrochloride plus sufentanil citrate inhibits glucose metabolism and epithelial‑mesenchymal transition in human esophageal squamous carcinoma KYSE30 cells by modulating the JAK/STAT3/HIF‑1α axis.

Dexmedetomidine hydrochloride (DEX-HCl) and sufentanil citrate (SFC) are commonly used anesthetic drugs for esophageal cancer (EC) surgery. The present study was performed to investigate the effect of DEX-HCl and SFC treatment on glucose metabolism and epithelial-mesenchymal transition in EC. Cell counting kit-8 (CCK8), clonogenic, wound healing and Transwell migration assays were performed to assess the effects of the DEX-HCl and SFC on KYSE30 cell proliferation, invasion and migration. Changes in lactate and glucose levels in KYSE30 cells were also detected. Western blot analysis was used to determine the protein expression levels of the JAK/STAT signaling pathway and glucose metabolism-related proteins. The results of CCK8, clonogenic and wound healing assays demonstrated that DEX-HCl and SFC inhibited KYSE30 cell proliferation, invasion and migration. Similarly, the combined DEX-HCl and SFC treatment significantly reduced lactate production, ATP production and glucose levels in KYSE30 cells. Western blotting indicated that DEX-HCl and SFC could reduce JAK/STAT and metastasis-related protein expression. Demonstrating a reduction in Hexokinase 2, matrix metallopeptidase 2 and 9, N-cadherin and lactate dehydrogenase A protein expression levels. The effects of DEX-HCl and SFC combined treatment were counteracted by the addition of JAK/STAT pathway activator RO8191, which suggested that DEX-HCl and SFC could serve a role in mediating the JAK/STAT signaling pathway in KYSE30 cells.

Retraction to: FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer.

Retraction to: FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer.

TPM3 mediates epithelial-mesenchymal transition in esophageal cancer via MMP2/MMP9.

BackgroundEsophageal cancer (EC) is a malignant tumor with high mortality. Correlations have been found between the expression level of tropomyosin 3 (TPM3) and the depth of tumor invasion, lymph node metastasis, and the 5-year survival rate. However, the specific mechanisms underlying EC remain unclear.MethodsStably transfected TPM3-overexpresing and TPM3-knockdown esophageal squamous cell carcinoma (ESCC) cell lines (ECa109 and EC9706) were constructed, and the association between TPM3 and the proliferation, invasion, and migration of ESCC was investigated using molecular biology methods. The associations between TPM3 and matrix metalloproteinase (MMP)2/9 or epithelial-mesenchymal transition (EMT)-related proteins were verified, and the potential tumor-promoting mechanism was explored by Gelatin Zymography Experiment.ResultsTPM3 was found to promote the proliferation, migration, and metastatic potential of ESCC in vivo and in vitro, and stimulate the expression of MMP2/9 and certain EMT markers other than E-cadherin. The replenishment of MMP2/9 restored the malignant behavior of ESCC caused by TPM3. A gelatinase assay showed that the expression of TPM3 was related to the activity of MMP9.ConclusionsTPM3 promoted proliferation, migration, and metastatic potential in EC cells. Additionally, TPM3 promoted the EMT process. This function may be achieved via the regulation the expression of MMP2/9.

FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer.

EC (esophageal cancer) is a common cancer among people in the world. The molecular mechanism of FAM196B (family with sequence similarity 196 member B) in EC is still unclear. This article aimed to clarify the role of FAM196B in EC. The expression of FAM196B in EC tissues was detected using qRT-PCR. The prognosis of FAM196B in EC patients was determined by log-rank kaplan-Meier survival analysis and Cox regression analysis. Furthermore, shRNA was used to knockdown the expression of FAM196B in EC cell lines. MTT, wound healing assays and western blot were used to determine the role of FAM196B in EC cells. In our research, we found that the expression of FAM196B was up-regulated in EC tissues. The increased expression of FAM196B was significantly correlated with differentiation, lymph node metastasis, stage, and poor survival. The proliferation and migration of EC cells were inhibited after FAM196B-shRNA transfection in vitro and vivo. The western blot result showed that FAM196B could regulate EMT. These results suggested that FAM196B severs as an oncogene and promotes cell proliferation and migration in EC. In addition, FAM196B may be a potential therapeutic target for EC patients.

Qigesan inhibits esophageal cancer cell invasion and migration by inhibiting Gas6/Axl-induced epithelial-mesenchymal transition.

Qigesan (QGS) has been used to effectively treat esophageal cancer (EC) for decades in China, but the mechanism by which it suppresses EC metastasis remains unknown. In this study, we examined the effects of QGS on EC cell mobility. Using immunohistochemistry and immunofluorescence, expression of Gas6 and Axl, which promote tumor cell migration and invasion, was examined in carcinoma tissues and adjacent normal tissues from EC patients. Levels of Gas6, Axl, and the Gas6/Axl complex were also examined in ECA109 and TE13 EC cells treated with QGS. In addition, immunofluorescent staining and quantitative protein analysis were used to examine E-cadherin, N-cadherin, and Snail levels in ECA109 and TE13 EC cells after QSG administration, and cell mobility was assessed. The results demonstrated that levels of Gas6 and Axl expression are higher in EC tissues than in adjacent normal tissues. Moreover, QGS decreased Gas6/Axl levels, increased E-cadherin expression, decreased Snail and N-cadherin expression, and inhibited epithelial-mesenchymal transition (EMT) in EC cells. QGS thus suppresses EMT in EC by inhibiting Gas6/Axl binding.

NDRG2 suppresses proliferation, migration, invasion and epithelial-mesenchymal transition of esophageal cancer cells through regulating the AKT/XIAP signaling pathway

N-Myc downstream-regulated gene 2 (NDRG2) has recently revealed as a candidate tumor suppressor gene. To inhibit tumor growth and decrease morbidity of esophageal cancer (EC), this study aims to test the hypothesis that the upregulation of NDRG2 may suppress proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of EC cells by regulating the AKT/XIAP signaling pathway. Immunohistochemistry was conducted for the identification of NDRG2, protein kinase B (p-AKT), X-linked inhibitor of apoptosis protein (XIAP) in EC tissues. To identify the regulatory mechanism of NDRG2 on the AKT/XIAP signaling pathway and EMT in EC, over-expressed lentiviral vector and shRNA were applied for up-regulating and interfering NDRG2 expression, and a series of determinations on the biological behavior of EC cells were performed to validate this regulation action. The results of immunohistochemistry showed NDRG2 was lowly expressed in EC tissues while p-AKT and XIAP are highly expressed. Over-expression of NDRG2 suppresses the proteins related to AKT/XIAP signaling pathway and EMT. Besides, a series of determinations shows the proliferation, migration and invasion of TE-13 cells were suppressed by over-expressed NDRG2, while the cell cycle progression was blocked and cell apoptosis was promoted. And in vivo experiment also demonstrated NDRG2 could inhibit tumor growth. Our findings demonstrate over-expression of NDRG2 works as tumor suppressive role in EC through its effects on inhibition of cell migration, invasion, and EMT by inhibiting the AKT/XIAP signaling pathway.

Upregulation of extracellular matrix metalloproteinase inducer promotes hypoxia-induced epithelial-mesenchymal transition in esophageal cancer.

Extracellular matrix metalloproteinase inducer (EMMPRIN) exerts important roles in tumor progression, including angiogenesis, metastasis and therapy resistance. The epithelial‑mesenchymal transition (EMT), which is induced by hypoxia, is an important process in cancer metastasis. However, the association between hypoxia and EMMPRIN remains to be elucidated in esophageal cancer. The expression of EMMPRIN was determined by western blotting and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and EMT markers were analyzed by western blotting, RT‑qPCR and immunofluoresence. The migration and invasion of cells was investigated by Transwell assay. The results indicated that the expression levels of EMMPRIN in esophageal cancer cells were markedly higher compared with those in normal esophageal cells. EMMPRIN was able to promote esophageal cancer cell migration and invasion under both hypoxic or normoxic conditions, as demonstrated by the migration and invasion assay. The expression levels of E‑cadherin were reduced, and those of snail family zinc finger 1, fibronectin, α‑smooth muscle actin and fibroblast secretory protein 1 increased in esophageal cancer cells following treatment with human recombinant EMMPRIN under hypoxic conditions. The mRNA expression levels of the EMT markers were similar to those of the protein expression levels. Furthermore, the results demonstrated that EMMPRIN was regulated by hypoxia‑inducible factor (HIF)‑1α. These data suggested that EMMPRIN promoted metastasis and the EMT in esophageal cancer cells by regulating HIF-1α.

Abstract 2297: Transcriptome profiling of invasion phenotype associated with epithelial-mesenchymal transition in esophageal cancer

Abstract The esophageal cancer (ESC) is one of the ten-leading cancers in Taiwan with highly metastatic potential. The aim of this study was to clarify relevant alterations of gene expression associated with the invasive phenotype of ESC. To reduce heterogeneity and to obtain data on genes specifically involved in invasive mechanism, we established a highly invasive ESC subline (CE48) through 10 passages of in vitro Matrigel selections. This subline exhibited increases of invasion and migration abilities with the ascending generations, in accompany of morphological alteration from epithelial type to mesenchymal type, suggesting an epithelial- mesenchymal transition (EMT) was occurred during this Matrigel selection. In support of this finding, five molecular EMT markers were also changed accordingly. Affymetrix cDNA microarray was used to compare the transcriptomes between the parental and the EMT-associated invasion subline. Heretical cluster and algorithmic analyses of the microarray dataset revealed that several functional pathways associated with these phenotypic alterations. On the other hand, 10 genes were examined for the potential differential expressions between parental and invasion subline by RT-PCR or western blot analysis. In which, TKT, FLNA, FN1, Gp96, Slug and IQGAP1 were found over-expressed in the invasion subline, suggesting a positive association in the regulation of EMT-associated invasion. Knockdown of TKT by siRNA further demonstrated suppression of cell invasion. Therefore, the EMT-associated invasion sublin and transcriptome profiling of the cells were determined. Results of this study provide molecular knowledge in the EMT-associated metastasis in ESC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2297.