The epithelial-mesenchymal transition phenotype of metastatic lymph nodes impacts the prognosis of esophageal squamous cell carcinoma patients

Wen, Jing; Luo, Kongjia; Liu, Qian Wen; Geng, Wenjing; Zhang, Mei Fang; Xie, Xiu Ying; Yang, Hong; Fu, Jianhua; Hu, Yi

doi:10.18632/oncotarget.9036

Cited by 20 publications

(22 citation statements)

References 29 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EMT serves a crucial role in cancer invasion, metastasis and progression (6,7). Although numerous EMT-associated markers have been reported to be effective prognostic factors for patients who have undergone curative resection in many types of digestive tumours, including esophageal, gastric, colorectal and hepatic carcinomas (11)(12)(13)(14), few studies have focused on the expression and prognostic value of EMT markers in ICC (15)(16)(17)(18)(19). Therefore, further investigation into the prognostic value and clinical significance of EMT in ICC is required.…”

Section: Discussionmentioning

confidence: 99%

“…A number of transcription factors, including Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug), Twist family BHLH transcription factor (Twist), Zinc finger E-box binding homeobox 1 (Zeb1) and Zeb2 , are also known to serve a central role in the activation of EMT (8)(9)(10). This process has been associated with tumor invasion, metastasis and a poor prognosis in various types of gastrointestinal tumor, including esophageal, gastric, colorectal and hepatic carcinomas (11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma

et al. 2019

View full text Add to dashboard Cite

The aim of the present study was to investigate the expression of epithelial mesenchymal transition (EMT)-associated proteins and their prognostic value in intrahepatic cholangiocarcinoma (ICC). The expression of six EMT-associated proteins, including E-cadherin, N-cadherin, Vimentin, Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug) and S100 calcium binding protein A4 (S100A4) was determined by immunohistochemistry in 109 patients with ICC who had received surgery. Survival analysis showed that patients with low E-cadherin expression (P<0.001) or high S100A4 (P<0.001) or Snail (P<0.001) expression had a reduced survival time. Based on the numbers of alterations in the expression of EMT-associated proteins as determined by immunohistochemical analysis, the patients were categorized as low (score, 0-3; n=75) or high (score, ≥4; n=34) EMT expression groups. The high EMT expression group was significantly associated with positive lymph node metastasis (P=0.023) and late Tumor-Node-Metastasis (TNM) stage (P<0.001). Furthermore, patients in the high EMT expression group had a significantly poorer overall survival time than those in the low EMT expression group (P<0.001). Multivariate analysis indicated that EMT status was a significant independent predictor for overall survival time (P=0.004), and was linked to surgical margin (P=0.013) and TNM stage (P<0.001). In conclusion, the reduced expression of E-cadherin and high expression of Snail and S100A4 were significantly associated with the poor survival of patients with ICC after surgery. The EMT protein expression status was associated with ICC progression, and may be considered as an independent prognostic indicator for patients with ICC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In gastric cancer, the expression of N-cadherin in metastatic lymph nodes was associated to a bad prognosis [ 54 ]. An other study related the heterogeneity between primary tumours and metastatic lymph nodes in oesophageal cancer, with distinct EMT phenotypes and thus, a novel independent prognostic indicator [ 55 ]. Similar results were found in head and neck cancer [ 56 ] and breast cancer [ 57 ].…”

Section: Emt In Cancermentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition and MicroRNAs in Lung Cancer

Legras

Pécuchet

Imbeaud

et al. 2017

Cancers

View full text Add to dashboard Cite

Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in tissue remodelling that was extensively studied as an actor of tumour progression, metastasis and drug resistance in many cancer types and in lung cancers. Here we described with an emphasis on NSCLC how the changes in signalling pathways, transcription factors expression or microRNAs that occur in cancer promote EMT. Understanding the biology of EMT will help to define reversing process and treatment strategies. We will see that this complex mechanism is related to inflammation, cell mobility and stem cell features and that it is a dynamic process. The existence of intermediate phenotypes and tumour heterogeneity may be debated in the literature concerning EMT markers, EMT signatures and clinical consequences in NSCLC. However, given the role of EMT in metastasis and in drug resistance the development of EMT inhibitors is an interesting approach to counteract tumour progression and drug resistance. This review describes EMT involvement in cancer with an emphasis on NSCLC and microRNA regulation.

show abstract

“…However, it is unclear whether ESCC patients can be divided into two groups based on the cells being epithelial- or mesenchymal-like. Recently, a study on the pathology of ESCC patients revealed that several phenotypes such as epithelial-like (E-cadherin: positive/vimentin- or N-cadherin: negative), mesenchymal-like (E-cadherin: negative/vimentin- or N-cadherin: positive), hybrid type (E-cadherin: positive/vimentin- or N-cadherin: positive), and null type (E-cadherin: negative/vimentin- or N-cadherin: negative) exist in ESCC patients [ 38 ]. Given that there have been no clinical investigations into the effects of EGFR inhibitors on ESCC patients based on epithelial- or mesenchymal-like phenotype, further clinical research is required.…”

Section: Discussionmentioning

confidence: 99%

Distinct effects of EGFR inhibitors on epithelial- and mesenchymal-like esophageal squamous cell carcinoma cells

Yoshioka

Ida

Nakai

et al. 2017

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundEpidermal growth factor receptor (EGFR) plays a pivotal role in the pathophysiology of esophageal squamous cell carcinoma (ESCC). However, the clinical effects of EGFR inhibitors on ESCC are controversial. This study sought to identify the factors determining the therapeutic efficacy of EGFR inhibitors in ESCC cells.MethodsImmortalized-human esophageal epithelial cells (EPC2-hTERT), transformed-human esophageal epithelial cells (T-Epi and T-Mes), and ESCC cells (TE-1, TE-5, TE-8, TE-11, TE-11R, and HCE4) were treated with the EGFR inhibitors erlotinib or cetuximab. Inhibitory effects on cell growth were assessed by cell counting or cell-cycle analysis. The expression levels of genes and proteins such as involucrin and cytokeratin13 (a squamous differentiation marker), E-cadherin, and vimentin were evaluated by real-time polymerase chain reaction or western blotting. To examine whether mesenchymal phenotype influenced the effects of EGFR inhibitors, we treated T-Epi cells with TGF-β1 to establish a mesenchymal phenotype (mesenchymal T-Epi cells). We then compared the effects of EGFR inhibitors on parental T-Epi cells and mesenchymal T-Epi cells. TE-8 (mesenchymal-like ESCC cells)- or TE-11R (epithelial-like ESCC cells)-derived xenograft tumors in mice were treated with cetuximab, and the antitumor effects of EGFR inhibitors were evaluated.ResultsCells were classified as epithelial-like or mesenchymal-like phenotypes, determined by the expression levels of E-cadherin and vimentin. Both erlotinib and cetuximab reduced cell growth and the ratio of cells in cell-cycle S phase in epithelial-like but not mesenchymal-like cells. Additionally, EGFR inhibitors induced squamous cell differentiation (defined as increased expression of involucrin and cytokeratin13) in epithelial-like but not mesenchymal-like cells. We found that EGFR inhibitors did not suppress the phosphorylation of EGFR in mesenchymal-like cells, while EGFR dephosphorylation was observed after treatment with EGFR inhibitors in epithelial-like cells. Furthermore, mesenchymal T-Epi cells showed resistance to EGFR inhibitors by circumventing the dephosphorylation of EGFR signaling. Cetuximab consistently showed antitumor effects, and increased involucrin expression in TE-11R (epithelial-like)-derived xenograft tumors but not TE-8 (mesenchymal-like)-derived xenograft tumors.ConclusionsThe factor determining the therapeutic effects of EGFR inhibitors in ESCC cells is the phenotype representing the epithelial-like or mesenchymal-like cells. Mesenchymal-like ESCC cells are resistant to EGFR inhibitors because EGFR signaling is not blocked. EGFR inhibitors show antitumor effects on epithelial-like ESCC cells accompanied by promotion of squamous cell differentiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0572-7) contains supplementary material, which is available to authorized users.

show abstract

The epithelial-mesenchymal transition phenotype of metastatic lymph nodes impacts the prognosis of esophageal squamous cell carcinoma patients

Cited by 20 publications

References 29 publications

Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma

Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma

Epithelial-to-Mesenchymal Transition and MicroRNAs in Lung Cancer

Distinct effects of EGFR inhibitors on epithelial- and mesenchymal-like esophageal squamous cell carcinoma cells

Contact Info

Product

Resources

About