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Cancer-associated Fibroblast Promotes Migration Of Human Breast Cancer Cells Via Activating The P38/MAPK Signaling Pathway

Posted on:2019-04-26Degree:MasterType:Thesis
Country:ChinaCandidate:L X FuFull Text:PDF
GTID:2394330566482521Subject:Biochemistry and Molecular Biology
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Objective : Breast cancer is a serious threat to women’s health.Cancer associated fibroblasts(CAF)has a strong ability of promoting migration,invasion,adhesion,and contraction in breast cancer cells.However,the mechanism is unclear.Therefore,this study intends to investigate the effects of CAF on cell migration in human breast cancer and explore its possible molecular mechanism.Methods:Effects of CAF on migration of BT549 and MDA-MB-231 were measured by transwell migration test after treated with CAF supernatant.Effects of CAF on migration related proteins E-cadherin and Vimentin were investigated by Western blotting after treated with CAF supernatant.After treating the human breast cancer cell line BT549 and MDA-MB-231 with CAF supernatant,SB203580 was used to inhibit the p38/MAPK pathway,then Transwell migration assay and Western blotting were used to detect the changes of migration and the expressions of E-cadherin and Vimentin in BT549 and MDA-MB-231 cells respectively.Results:CAF promoted the migration of BT549 and MDA-MB-231 breast cancer cells,inhibited the expression of E-cadherin and up-regulated the expression of Vimentin in BT549 and MDA-MB-231 cells.CAF activated the p38 /MAPK signaling pathway of BT549 and MDA-MB-231 breast cancer cells and promoted the expression of p-P38 protein.The ability of CAF to promote the migration of BT549 and MDA-MB-231 cells was significantly inhibited,and the expression of E-cadherin protein was up-regulated while the expression of Vimentin protein was down-regulated after SB203580 inhibiting the p38/MAPK pathway.Conclusions: Simulated tumor microenvironment by CAF cultured supernant,we demonstrate that CAF has strong ability of promoting cell migration in human breast cancer cells.And the molecular mechanism may be through activating p38/MAPK signal pathways via down-regulating E cadherin and up-regulating Vimentin.This study can help futher reveal the mechanism of tumor development and metastasis in breast cancer.
Keywords/Search Tags:Breast cancer, Cancer-associated fibroblast, Cell migration, p38/MAPK signaling pathway
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