Objective To investigate the structure characteristics， functions， and research progress of Notch signaling pathway in digestive tumors. Methods The related literatures about the molecular genetic mechanism of Notch signaling pathway were reviewed. Results The Notch signaling pathway plays an important role not only in normal cells’ growth， differentiation， proliferation， and apoptosis but also in a variety of tumors’ occurrence and development. Conclusion The reasonable regulation to Notch signaling pathway may open up new ways to the treatment of the tumor.
Objective To investigate the prognostic value of epithelial-mesenchymal transition （EMT） related proteins （Snail， E-cadherin， and N-cadherin） in gastric cancer and its relationship with tumor initiating cells （TICs） marker （CD133）. Methods The expressions of EMT-related proteins and CD133 protein in the gastric cancer tissues and normal gastric mucosa tissues adjacent to gastric cancer were detected by Western blot method. The relations between the expressions of EMT-related factors proteins and CD133 protein and the clinicopathologic characters were analyzed. The correlations between EMT-related factors and CD133 were analyzed by Spearman. The correlations between EMT-related factors expressions and CD133 expression and survival were analyzed by Kaplan-Meier method and Log-rank test. Results ① The protein expression levels of Snail， N-cadherin， and CD133 in the gastric cancer tissues were significantly higher than those in the normal gastric mucosa tissues adjacent to gastric cancer （Snail：0.599±0.114 versus 0.259±0.108， P=0.020；N-cadherin：0.754±0.154 versus 0.329±0.134， P=0.001；CD133：0.635±0.119 versus 0.485±0.116， P=0.029）， while the protein expression level of E-cadherin was lower than that in the normal gastric mucosa tissues adjacent to gastric cancer （0.378±0.123 versus 0.752±0.156， P=0.003）.② The expression levels of Snail and N-cadherin in the gastric cancer patients with vascular invasion， lymphatic vessel invasion，N3 lymph node metastasis， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph node metastasis， diameter less than 5 cm， andⅠ＋Ⅱ staging（P＜0.05）， while E-cadherin protein expression was lower than that in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph nodes metastasis， andⅠ＋Ⅱstaging （P＜0.05）. The expression levels of CD133 in the gastric cancer patients with lymphatic vessel invasion， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without lymphatic vessel invasion， diameter less than 5 cm， andⅠ＋Ⅱ staging （P＜0.05）. ③The Snail and N-cadherin protein expressions were significantly positive correlated with CD133 protein expression， respectively （rs=0.278， P=0.048；rs=0.406， P=0.003）， while E-cadherin protein expression was significantly negative correlated with CD133 protein expression （rs=-0.504， P=0.000）.④ The survival time in the patients with lower expressions of Snail， N-cadherin， and CD133 were significantly longer than those in the patients with higher expressions of Snail， N-cadherin， and CD133 （P＜0.05）. The combination of Snail， N-cadherin， E-cadherin， and CD133 could effectively predict survival. Conclusions There is a significant correlation between EMT and gastric cancer TICs， and which are correlated with aggressive clinicopathologic features of gastric cancer. The combination of Snail， E-cadherin， N-cadherin， and CD133 may be effectively predict the prognosis of gastric cancer patients.
Hypoxic microenvironment always exists in solid tumors, and it closely relates to the development and metastasis of solid tumor. As a main transcription factor responding to hypoxic environment, hypoxia-inducible factor (HIF) can promote tumor cell proliferation, survival, angiogenesis, and epithelial-mesenchymal transition (EMT), etc. EMT is a biological process that epithelial phenotype was transformed into mesenchymal phenotype, which is mainly associated with its signaling pathways, transcription factors, inflammatory factors and miRNAs, and plays a vital role in tumor invasion and metastasis. This paper summarizes the effects of hypoxia signaling pathway, Wnt/β-catenin signaling pathway, Notch signaling pathway, NF-κB signaling pathway, Hedgehog (Hh) signaling pathway and PI3K/Akt signaling pathway on the EMT of tumor cells.
ObjectiveTo study the relationship between mesenchymal transition epithelial (EMT) and the occurrence, development, invasion, and metastasis of gastric cancer, and to seek to block the EMT process so as to achieve the purpose of treating tumor. MethodsThe literatures of EMT, signal pathway, and gastric cancer were analyzed by querying the PubMed. ResultsThe function and regulation mechanism of EMT is closely related to the development of gastric cancer, in the growth and proliferation of gastric cancer, tumor invasion and metastasis through a variety of signaling pathways play a role, with a great clinical application prospects. ConclusionsEMT and tumor metastasis is very close, almost involved in every process of metastasis. It is necessary to further study the relationship between EMT and cancer, including gastric carcinoma metastasis. A new way for the treatment of human gastric cancer.
ObjectiveTo investigate the relationship of epithelial mesenchymal transition (EMT) related proteins expressions in invasive ductal carcinoma of breast to its clinicopathologic features and prognosis. MethodsThe expressions of EMT related proteins (Vimentin, E-cadherin, and MMP2) in the 118 cases of invasive ductal carcinoma of breast and 30 cases of corresponding normal breast tissues adjacent to cancer were detected by immunohistochemistry. The relationship of EMT related proteins expressions to age, tumor site, tumor size, lymph node metastasis, histological grade, TNM stage or prognosis of the patients with invasive ductal carcinoma of breast was analyzed. Results①The positive rates of the Vimentin protein and MMP2 protein in the invasive ductal carcinoma of breast were significantly higher than those in the corresponding normal breast tissues adjacent to cancer﹝Vimentin protein: 50.8% (60/118) versus 10.0% (3/30), P < 0.05; MMP2 protein: 63.6% (75/118) versus 6.7% (2/30), P < 0.05﹞, the positive rate of E-cadherin in the invasive ductal carcinoma of breast was significantly lower than that in the corresponding normal breast tissues adjacent to cancer ﹝56.8% (67/118) versus 93.3% (28/30), P < 0.05﹞.②The positive rate of the Vimentin protein expression in the invasive ductal carcinoma tissue was positively related with the lymph node metastasis and TNM staging (rs=0.346, P < 0.05; rs=0.231, P < 0.05). The positive rate of the E-cadherin or MMP2 protein expression was negatively or positively related with the tumor size, lymph node metastasis, histological grade, and TNM stage (E-cadherin: rs=-0.444, P < 0.05; rs=-0.493, P < 0.05; rs=-0.323, P < 0.05; rs=-0.474, P < 0.05. MMP2: rs=0.361, P < 0.05; rs=0.434, P < 0.05; rs=0.396, P < 0.05; rs=0.376, P < 0.05).③The Kaplan-Meier survival curve analysis showed that the positive expressions of Vimentin and MMP2 were stronger, the tumor free survival time was shorter (P < 0.05), and the positive expression of E-cadherin was stronger, the tumor free survival time was longer (P < 0.05). ConclusionJoint detection of EMT related proteins (Vimentin, E-cadherin, MMP2) of invasive ductal carcinoma tissue of breast could predict the pathological grade and clinical stage, as well as effective prognosis of patients with invasive ductal carcinoma of breast in clinical.
Objective To explore the effectiveness of the transforming growth factor-β1(TGF-β1) and tumor necrosis factor-α(TNF-α) inducing human bronchial epithelial(HBE) cells to optimize epithelia-mesenchymal transformation(EMT) model. Methods Blank control, TGF-β1 10 ng/ml, TNF-α 10 ng/ml, TGF-β1 10 ng/ml+TNF-α 10 ng/ml induced human epithelial cells for 24 hours. Then the change of morphological alteration were observed by applying CCK8, cells migration assay and Western blot technique. Results When TGF-β1 plus TNF-α induced human epithelial cells for 24 hours, most of HBE cells traits changed including morphological alteration from cobblestone to fusiform, connection between cells vanishing, intercellular space broadening. In the experiments of checking cell migration capacity by the vitro scratch test, the group spacing was 420.06±10.38 μm in the blank control group, 499.86±34.00 μm in the TGF-β1 10 ng/ml group, 514.93±10.56 μm in the TNF-α 10 ng/ml group, 569.68±33.58 μm in the TGF-β1 10 ng/ml+TNF-α10 ng/ml group. TGF-β1 cooperated with TNF-α led to scratch spacing narrowing significantly. Western blot analysis showed that expression of E-cadherin and Vimentin varied significantly in the TGF-β1+TNF-α group. Conclusion Inducing human bronchial epithelial cell by TGF-β1 cooperated with TNF-α optimizes EMT model.
Objective To summarize research status and mechanism about effects of carcinoma-associated fibroblasts (CAFs) on breast cancer stem cells. Method Relevant literatures about the relationship between the CAFs and breast cancer stem cells were collected and reviewed. Results CAFs were the majority type of the breast cancer stromal cells. The cancer stromal cell was also the important part of the tumor microenvironment, which could promote the proliferation, adhesion, invasion, and metastasis of the breast cancer. A subpopulation of cancer stem cells with the potentials of self-renewal and multi-directional differentiation in the breast cancer tissues might cause the tumor development. There was a phenotypic heterogeneity in the beast cancer stem cells, it was related to the tumor recurrence and therapy resistance. The CAFs could promote the formation of breast cancer stem cells through the epithelial mesenchymal transition and promote the transformation of tumor stem cell phenotype. More research needed to be done to prove these processes. Conclusion CAFs play an important role in formation of breast cancer stem cells and transformation of tumor stem cell phenotype, which might provide a new idea about treating breast cancer.
ObjectiveTo investigate the effect of eukaryotic initiation factor 6 (eIF6) expression on invasion and metastasis of colorectal cancer cells and Wnt/β-catenin signaling pathway.MethodsImmunohistochemistry was used to detect the expressions of eIF6 protein in colorectal cancer tissues and paracancerous tissue. Sw837 cell lines with overexpression/knockdown eIF6 were constructed by transfection and divided into control group, empty plasmid group, overexpression group and knockdown group respectively. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blotting (WB) were used to verify the overexpression/knockdown of eIF6 in sw837 cells. WB was used to detect the expressions of β-catenin, glycogen synthase kinase-3β (GSK-3β), anaphase promoting complex (APC), zinc finger transcription factor SNAI (Snail), E-cadherin and Vimentin. Transwell invasion test, Scratch test and subcutaneous tumorigenesis test were used to detect the migration ability, invasion ability and tumorigenesis ability in vivo of cells. The pathological changes of the transplanted tumor were observed by HE staining.ResultsThe positive expression rate of eIF6 protein in cancer tissues was significantly higher than that in adjacent tissues (P<0.05). Compared with those in the control group, the protein expression levels of β-catenin, Snail and Vimentin in the overexpression group were higher, the protein levels of GSK-3β, APC and E-cadherin were lower, the ability of cell migration and invasion, and tumorigenicity in vivo were enhanced, the difference were statistically significant (P<0.05). The protein expression levels of β-catenin, Snail and Vimentin were lower in knockdown group, the protein levels of GSK-3β, APC and E-cadherin were higher, the ability of cell migration and invasion, and tumorigenicity in vivo were reduced, the difference were statistically significant (P<0.05).ConclusioneIF6 may promote the invasion and metastasis of colorectal cancer cells by activating Wnt/β-catenin signaling pathway.
ObjectiveTo understand the research progress of the matrix metalloproteinases (MMPs) family in regulating the development of hepatocellular carcinoma (HCC) and its mechanism, in order to provide a reference for the basic research and clinical diagnosis and treatment of HCC. MethodThe relevant literature on the regulation of HCC occurrence, development, and mechanisms by MMPs both domestically and internationally in recent years was reviewed. ResultsThe extracellular matrix (ECM) microenvironment of HCC cells determined the invasiveness and degree of metastasis of tumor cells. The degradation and remodeling of ECM during epithelial mesenchymal transition (EMT) were the main factors contributing to the invasion and metastasis of HCC. The abnormal expression of most members of the MMPs family could lead to ECM breakdown, cell invasion and attachment, and markedly accelerate the process of EMT, thereby promoting the invasion and metastasis of HCC cells. At present, there were many MMPs related to the development of HCC, including MMP-1, 2, 3, 7, 9, 12, 13, 14. The relevant research on the relation between MMP-8, 10, 11, 15, 16, 20, 21, 26 or 28 and the development of HCC was relatively limited, while the exact research on the relationship between the MMP-17, 19, 23, 24, 25 or 27 and HCC development had not been retrievaled. ConclusionsThe MMPs family members (especially MMP-2, 3, 7, 9, 10, 12) play a crucial role in the progression of HCC, including proliferation, invasion, and metastasis. Further exploration of the potential intrinsic relation between all members of the MMPs family members and the development of HCC is crucial for predicting HCC metastasis potentiality and prognosis, as well as developing new or improved targeted anti-cancer therapies for HCC.