The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma

Abstract

The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1alpha-TGF-beta1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.

Expression and function role of DNA methyltransferase 1 in human bladder cancer

“…24 At the molecular marker level, epithelial‐mesenchymal transition is characterized by loss of E‐cadherin and increased expression of transcription repressors of E‐cadherin including Snail. 31‐34 We demonstrated that a DNMT1 silencing vector induced increases in E‐cadherin and a decrease in vimentin, Snail, and MMP‐9 in bladder cancer cells. On the basis of these findings, the changes in epithelial‐mesenchymal transition might be responsible for the increased invasiveness in DNMT1‐positive urothelial cancers.…”

IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus

“…Data obtained from cell and xenograft tumor growth experiments revealed that inhibiting IL-6 resulted in slower tumor growth and reduced invasiveness. The transformation of an epithelial cell into a mesenchymal cell appears to be functionally relevant to the invasive characteristics of epithelial tumors, including esophageal cancer [19,29,30]. At the molecular marker level, EMT is characterized by the loss of E-cadherin and increased expression of invasion-related factors [31].…”

The Prognostic Impact of TGF-β1, Fascin, NF-κB and PKC-ζ Expression in Soft Tissue Sarcomas

“…Another possibility is TGF-β induced systemic immune suppression [27]. The TGF-β pathway activation has been shown to negatively influence prognosis both in epithelial [28], [29] and in mesenchymal bone [30] and soft tissue tumors [18], [21], [31]. The latter studies, however, are devoted to one particular STS type, while investigations of TGF-β1 expression by whole-array human STS with concern to impact on survival are not reported.…”