Reasarch On The Mechanism Of STMN1 Gene In Migration And Chemotherapy Of Esophageal Squamous Cell Carcinoma

Esophageal cancer is one of most common cancer in the world.It's hard to detect the early symptom.Lymph node metastasis commomly occurs in esophageal cancer patients,which indicate poor prognosis.Recent studies have revealed that stathmin is highly expressed in many cancersand associated with relevant clinical parameters such as lymph node metastasis,pathological grade,poor prognosis,chemoresistance.However,mechanisms of stathmin in promoting esophageal cancer progression remain largely unknown and need to be further elucidated.This dissertation consists of two parts.The first part of the dissertation demonstrate that stathmin promotes esophageal cancer cell invasion and metastasis in vitro and in vivo.Based on previous proteomic results in our lab,it revealed that stathmin was overexpression in ESCC tissues using 2-DE and immunohistochemistry western blotting.We found that serum levels of stathmin were significantly elevated in esophageal cancer patients by ELISA,significantly correlated with lymph node metastasis,histological grad and tumor size in ESCC.Overexpression stathmin cell lines were established by transfection.We discovered that stathmin overexpression promoted the invision and migration of esophageal cancer cells via transwell and wound healing assays.Some adhesion associated genes,such as LYPD3,CLCA2,CEACAM5,FAK,RASSF5,FN,KRT6C,KRT15,KRT17 and KRT13 were significantly increased in stathmin overexpression cell using transcriptome assay and real-time PCR.Overexpression of stathmin significantly facilitated the adhesion ability of esophageal cancer cells to extracellular matrix by adhesion assay.The expression of integrin?5?1,FAK,P-ERK and keratin 17 protein significantly increased in stathmin overexpression cell lines by western bloting,but not for integrin?3,?4,vinculin and ERK.The integrin?5?1,FAK and P-ERK greatly decreased in knockdown of stathmin group compared with the control.Together these results,our data demonstrate an important role for stathmin in increasing ESCC cell invasion and migration,and indicate that up-regulation of integrina5pl/FAK/ERX pathway may contribute to ESCC cell metastasis.In the second part of the dissertation reveal that overexpression of stathmin enhanced the resistance of esophageal cancer cells to paclitaxel.Stathmin has an activity that regulates microtubules in cells.By constructing stably overexpression stathmin cell lines,we found that stathmin overexpression significantly enhanced the resistance of esophageal cancer cells to paclitaxel in the same conditions.The apoptosis rate of esophageal cancer cell decrease in stathmin overexpression cell line.Caspase8 and caspase9 cleavage fragments were found by western blot.There is no change about autophagy-related molecules such as LC3,BNIP3.