Objective To summarize the roles of tumor initiating cells （TICs） and epithelial-mesenchymal transition （EMT） in tumor metastasis and drug resistance. Methods Domestic and international publications online which involving TICs，EMT，and its roles in tumor metastasis and drug resistance in recent years were reviewed. Results TICs were self-renewal cells and had the ability to give rise to more differentiated cell types，and played an important role in tumor metastasis and drug resistance. Various markers had been used to identify TICs，such as CD133，CD44，and so on. EMT was the process by which epithelial cells losed polarity and detach from the epithelial sheet， and acquired a motile mesenchymal phenotype，usually observed in embryo development and wound healing. It also could promote tumor progression and metastasis，and may also be responsible for the ability of tumors to evade the body’s immune response. EMT may be the reasons of TICs that drived tumor metastasis and recurrence. TICs or EMT as a target for treatments may effectively prevent tumor recurrence and improve patient’s survival. Conclusions EMT is probably the mechanism that TICs promote tumor metastasis and drug resistance. More effective target therapies for cancer may be found if we know more about TICs and EMT.
ObjectiveTo summarize the role of epithelial-mesenchymal-transition （EMT） in occurrence and development of gastrointestinal cancer. MethodsDomestic and international publications online involving EMT of gastrointestinal cancer in recent years were collected and reviewed. ResultsEMT was a highly conserved process that has been well characterised in embryogenesis. Studies had shown that the aberrant activation of EMT in adult epithelia could promote tumour metastasis by repressing cell adhesion molecules. E-cadherin， one of the epithelial cell markers, maybe involved in the process of the EMT, especially of the Ecadherin transcriptional repressors， these transcriptional repressors significantly increased in the gastrointestinal cancer. Further more， EMT might involve in the process of gastrointestinal cancer stem cells formation. ConclusionsEMT and it’s regulators play a very important role in gastrointestinal cancer， and may provide a newsight into the gastrointestinal cancer. It also can provide a novel clinical targets to treat the gastrointestinal cancer.
ObjectiveTo understand research progress of influence of claudins on proliferation and activation for breast cancer. MethodThe relevant literatures of influence of claudins on proliferation and activation for breast cancer were retrieved and reviewed. ResultsThe claudins had 24 members in mammals,claudin-13 was missing in human beings.Expression and distribution mode of the claudins possessed highly tissue-specific,and multiple proteins were expressed in many organizations.The expressions of claudins could be regulated from the levels of transcription and post-transcription,coordinately regulated by the transcription factor and post-synthetic modifications.Claudins were related to epithelial-mesenchymal transition.Now the studies were relatively clear those focused on claudin-1,-2,-4,-6,and other subtypes,and the expression of claudin-1 indicated the poor prognosis of tumor;claudin-2 was closely related to liver metastasis of breast cancer;claudin-4 was closely related to triple negative breast cancer;the function of claudin-6 in the breast cancer was controversial.In addition to the claudins mentioned above,other claudin members also played certain roles in normal breast and malignant breast tumors.Claudin-5 might participate in metastasis of breast cancer through N-WASP and ROCK signal pathway;CD-24 and claudin-7 immunodepression had a certain guiding significance on prognosis of invasive ductal carcinoma;the expressions of claudin-16 and HAPLN3 gene were remarkably increased in human breast cancer;Claudin-20 induced breast cancer cells into a subtype that possessed the high invasiveness and weakened the resis-tance of epithelial-mesenchymal transition.Recently,the claudin-low subtype was proposed,and it differed from other types of breast cancer in many aspects,and also it had a better prognosis than other types of triple negative breast cancer. ConclusionsClaudin,being an important member of tight junction protein,is confirmed to be related to epithelial-mesenchymal transition.Claudins play important roles in dissociaton,activation,invasiveness,and metastasis of breast cancer,but there is no final conclusion which member contributes to invasiveness and metastasis of breast cancer.Moreover,there are opposite conclusions on some certain claudins members in breast cancer which might due to the different subtypes of breast cancer,so,further studies about the function of claudins in different subtypes are needed eagerly.
ObjectiveTo explore the effectiveness of Ovol2 gene for epithelial-mesenchymal transition (EMT) to offer some theory evidences for the targeted therapy in lung adenocarcinoma. MethodsA549 cells were treated with control and Ovol2 overexpressioned by lentivirus infection. Real-time PCR were performed to test the mRNA level of genes correlated to EMT. Western Blot was performed for protein level of the following makers:E-cadherin, N-cadherin, vimentin, ect. Moreover, we tested the migration and invasion ability of A549 cells by transwell and wound healing experiment. ResultsAfter treated with Ovol2 overexpressed, the expression level of E-cadherin raised, while the expression level of N-cadherin, vimentin and Twist1 declined in both mRNA and protein expression level. The results of wound healing and transwell experiment indicated that the migration and invasion ability of A549 cells weakened. ConclusionOverexpression of Ovol2 gene can suppress the distant metastasis ability and invasion ability of A549 cells by inhibiting the EMT.
ObjectiveTo investigate the role of GOLPH3 in esophageal squamous cell carcinoma (ESCC). MethodsWound healing assays, transwell invasion assays and 3D culture were carried out to analyze the cell migration and invasion ability of GOLPH3 overexpression and knockdown KYSE-140 cells. The relationship between GOLPH3 expression and CYR61, CD44 and Snail mRNA expression was further examined through qRT-PCR, to identify the mechanisms involved. ResultsGOLPH3-promoted ESCC cell migration and invasion. CYR61, CD44 and Snail mRNA expression levels were correlated with GOLPH3 protein expression level. ConclusionGOLPH3 overexpression promotes ESCC metastasis through epithelial-mesenchymal transition (EMT), and plays an oncogenesis role in ESCC.
Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
This study aims to investigate the effect of substances secreted or metabolized by vascular endothelial cells on epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells under indirect co-culture condition. Human hepatocellular carcinoma cell line QGY-7703 was cultured in vitro, and then was co-cultured with conditioned medium of human umbilical vein endothelial cells (HUVEC). The morphological changes of QGY-7703 cells were observed by inverted phase contrast microscopy. The migration ability of QGY-7703 cells was analyzed by scratch-wound assays. The effect of conditioned medium on the expression and distribution of EMT related proteins was detected by Western blot and immunofluorescence assays, respectively. The results showed that the QGY-7703 cells gradually changed from polygonal to spindle shape, the migration ability promoted significantly, and both the expression and distribution of EMT related marker changed in a time-dependent manner after co-culturing. The results confirm that vascular endothelial cells can induce EMT in hepatocellular carcinoma cells under indirect co-culture condition.
Objective To explore whether blood exosome carrying miR-140-3p can regulate the malignant progression of small cell lung cancer (SCLC) through targeting ubiquitin-conjugating enzyme E2C (UBE2C). MethodsThis study was consisted of bioinformatics analysis, clinical research, cell analysis, and animal experiments. We searched GEO database for data of SCLC related microRNA (miRNA) dataset GSE19945, mRNA dataset GSE40275, and GSE60052. T-test was used to detect the differential expression of miR-140-3p in normal tissues and SCLC tissues in the dataset, and the expression of miR-140-3p in different tissues and extracellular vesicles was analyzed through a database. SCLC tissue and paired cancerous tissues excised at Yongzhou Central Hospital were collected between December 2021 and December 2022, and healthy volunteers 7 days before the start of the study was selected. Quantitative real-time polymerase chain reaction was used to detect the expression level distribution of miR-140-3p and UBE2C in tissue samples of SCLC patients and healthy volunteers. SCLC patients were divided into low expression and high expression groups based on the median expression level, and the correlation between the expression levels of miR-140-3p and UBE2C and patient pathological parameters was analyzed. 20 male nude mice was selected. The nude mice were randomly divided into 4 groups: miR-140-3p, UBE2C analog negative control group, and analog control group, with 5 mice in each group. Immunohistochemical detection system was used to detect tumor tissue sections in nude mice. Results A total of 45 patients and 30 healthy volunteers were included. SCLC malignant progression was significantly associated with the expression of miR-140-3p and UBE2C. The expression of miR-140-3p was low in blood-derived exosomes from SCLC patients. Overexpression of miR-140-3p inhibited the proliferation (47.33±2.52 vs. 107.67±10.69, P<0.05), migration [(11.63±2.62)% vs. (31.77±4.30)%, P<0.05] and invasion (44.33±3.06 vs. 102.67±8.50, P <0.05) and promoted their apoptosis [(14.48±1.20)% vs. (10.14±1.21)%, P<0.05]. Bioinformatics analysis yielded the target gene UBE2C of miR-140-3p. In vitro experiments further demonstrated that miR-140-3p directly targetd UBE2C to inhibit SCLC cell proliferation, migration, invasion, epithelial mesenchymal transition, and promote apoptosis. Mouse xenotransplantation experiments showed that miR-140-3p mimic significantly inhibited tumor growth. ConclusionTherefore, the miR-140-3p extracellular vesicle and the oncogenic gene UBE2C may be potential targets for inhibiting the malignant progression of SCLC.