ABSTRACT
Erythropoietin-producing hepatoma (EPH) receptors are considered the largest family of receptor tyrosine kinases and play key roles in physiological and pathologic processes in development and disease. EPH receptors are often overexpressed in human malignancies and are associated with poor prognosis. However, the functions of EPH receptors in epithelial-mesenchymal transition (EMT) remain largely unknown. This review depicts the relationship between EPH receptors and the EMT marker E-cadherin as well as the crosstalk between EPH receptors and the signaling pathways involved EMT. Further discussion is focused on the clinical significance of EPH receptors as candidates for targeting in cancer therapeutics. Finally, we summarize how targeted inhibition of both EPH receptors and EMT-related signaling pathways represents a novel strategy for cancer treatment.
Subject(s)
Antineoplastic Agents , Epithelial-Mesenchymal Transition , Neoplasms , Receptors, Eph Family/physiology , Signal Transduction , Cadherins , Humans , Receptor Protein-Tyrosine KinasesABSTRACT
This study aims to investigate the expression and significance of EphA2 and EphrinA-1 in human gastric adenocarcinoma progression and prognosis. The expression of EphA2 and EphrinA-1 was detected in the cell lines and tissues of gastric adenocarcinoma. Different expression levels of EphA2 and EphrinA-1 were found in two cell lines. The expression of EphA2 and EphrinA-1 was significantly higher in gastric adenocarcinoma tissues than in normal tissues. Statistical analysis showed a significant correlation of EphA2 expression with the depth of tumor invasion, tumor-node-metastasis (TNM) stages, and lymph node metastasis. EphrinA-1 over-expression was significantly correlated with TNM stages and lymph node metastasis, while EphA2 expression was found to be an independent prognostic factor of postoperative gastric adenocarcinoma. In conclusion, the increased expression of EphA2 and EphrinA-1 plays an important role in the progression of human gastric adenocarcinoma, in which elevated EphA2 expression is an independent factor that indicates poor prognosis in postoperative gastric adenocarcinoma.
Subject(s)
Adenocarcinoma/metabolism , Ephrin-A1/metabolism , Receptor, EphA2/metabolism , Stomach Neoplasms/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Cell Line, Tumor , China/epidemiology , Female , Humans , Male , Middle Aged , Postoperative Period , Prognosis , Stomach/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathologyABSTRACT
OBJECTIVE: To investigate the expressions of homeobox transcription factor-2 (CDX(2)) and E-cadherin and their relations to the clinicopathological characteristics of gastric carcinoma. METHODS: Immunohistochemistry was performed on 83 human gastric carcinoma specimens and 40 normal gastric mucosa specimens for examining the expressions of CDX(2) and E-cadherin, and the relations of their expression with the tumor differentiation, infiltration and metastasis were analyzed. RESULTS: According to the LaurAn classification, the positive expression rate of CDX(2) in intestinal type of gastric carcinoma was 56.86%, and 34.38% in the diffuse type, showing significant difference between the two types (P<0.05). The positivity rate of E-cadherin was also significantly different between the two types (66.67% vs 28.13%, P<0.01). In regard to tumor differentiation, the positivity of CDX(2) and E-cadherin expressions was significantly different between moderately to well differentiated tumors and poorly differentiated ones (P<0.01). The tumors infiltrating mucosal and submucosal layers were significantly different from those infiltrating the muscular and serous membrane layer in the positivity of CDX(2) and E-cadherin expressions (P<0.01), which were also different for the presence of lymph node metastasis (P<0.05). Regression analysis did not reveal significant correlations between CDX(2) and E-cadherin expression in gastric carcinoma (P>0.05). CONCLUSION: The abnormal expression of CDX(2) and E-cadherin plays an important role in the development of gastric carcinoma, especially the intestinal type. CDX(2) and E-cadherin may serve as useful markers to predict the prognosis of patients with gastric carcinoma.
Subject(s)
Cadherins/metabolism , Homeodomain Proteins/metabolism , Stomach Neoplasms/pathology , Adult , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , CDX2 Transcription Factor , Cadherins/genetics , Female , Homeodomain Proteins/genetics , Humans , Male , Middle Aged , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolismABSTRACT
BACKGROUND & OBJECTIVE: Some research showed that carcinoembryonic antigen(CEA) related to cell adhesion and cyclooxygenesis 2(COX2) may be related to colorectal carcinogenesis. This study was designed to investigate the expression of CEA and COX2 to evaluate their effects on the tumorigenesis and progression in the colorectal cancer. METHODS: The immunohistochemistry was used to determine the expression of CEA and COX2 in the 34 tissues of colorectal cancer,border of cancer, normal mucosa,and 19 metastatic lymph nodes. RESULTS: CEA expression level had a correlation with the differentiation of the tumor tissue (P< 0.05), but had no correlation with lymph node metastasis,Dukes' stage,the patients' age,sex,and the location of tumor (P >0.05). The level of COX2 increased in the majority of tumor tissues (31/34) and all of the lymph node metastases, but had no correlation with the tumor differentiation, stage,location,patients' age and sex(P >0.05). There was significant difference of expression of CEA and COX2 between tumor and nontumor tissues (P< 0.01). CONCLUSION: The abnormal expression of CEA and COX2 plays a role in the carcinogenesis and development of colorectal cancer.
