WNT5A与小细胞肺癌临床特征的相关性研究及其对细胞迁移作用的影响  

High expression of WNT5A in small cell lung cancer and promotion of cell migration by phosphorylation of JNK

作　　者：魏巍[1] 赵晓亮[1] 苏延军[1] 尤健[1] 张真发[1] 王勐[1] 宫立群[1] 张振[1] 张彬[1] 王长利[1] Wei WEI Xiaoliang ZHAO Yanjun SU Jian YOU Zhenfa ZHANG Meng WANG Liqun GONG Zhen ZHANG Bin ZHANG Changli WANG(Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tian- jin Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, Chin)

机构地区：[1]天津医科大学肿瘤医院肺部肿瘤科,国家肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心,天津市300060

出　　处：《中国肿瘤临床》2017年第1期46-51,共6页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金项目(编号:81470137);天津市抗癌重大专项(编号:12ZCDSY15400);天津医科大学科学基金项目(编号:2014KY209)资助~~

摘　　要：目的:检测WNT5A在小细胞肺癌(small cell lung cancer,SCLC)中的表达及其促细胞迁移作用的机制。方法:采用免疫组化的方法检测79例SCLC和25例正常肺组织中WNT5A的表达量。通过细胞划痕和Transwell小室检测WNT5A及JNK对SCLC细胞系DMS153迁移能力的作用,应用Western blot检测干扰WNT5A后磷酸化JNK含量的变化。结果:WNT5A在SCLC中表达高于正常肺组织,并且与肿瘤的临床分期、淋巴转移及远处转移相关,WNT5A的表达与神经元特性烯醇化酶(NSE)、胃泌素释放肽前体(Pro-GRP)也有明显相关性。干扰WNT5A导致DMS153迁移能力下降,应用JNK抑制剂SP600125能够阻止WNT5A造成的细胞迁移增加。结论:WNT5A在SCLC中高表达,并且与肿瘤的转移相关,WNT5A通过磷酸化JNK促进SCLC细胞迁移,并且可以作为SCLC的预测指标和治疗靶点。Objective： The expression of WNT5A is associated with aggressive tumor biology and poor clinical outcomes of various types of cancer. However, its function in the cell migration of small cell lung cancer （SCLC） should be elucidated. Methods： The expres- sion of WNT5A in SCLC and normal lung tissues was detected by immunohistochemisty. The correlation between the expression and clinical characteristics of WNTSA was analyzed. The function of WNT5A in regulating cell migration was studied in DMS253 cell line in vitro. Small interfering RNA （SiRNA） was used to knock down WNT5A. Wound healing and Transwell tests were used to determine the migration rate of DMS153. The phosphorylated JNK expression was detected by Western blot analysis. Results： The WNTSA expression was higher in SCLC tissues than that of normal lung tissues. WNT5A was correlated with clinical stages, lymph nodes, and distance me- tastasis in SCLC. The high expression of WNT5A was accompanied by abnormal levels of NSE and Pro-GRR The WNT5A phosphoryla- tion of JNK promoted cell migration in vitro. Conclusion： The expression of WNT5A in SCLC is high and correlated with tumor metasta- sis. The influence of WNT5A/JNK on the cell migration property of DMS153 supports the concept that WNT5A can initiate the cell mi- gration of SCLC, which suggested that WNTSA may be a marker and can be potentially used as an effective therapeutic target for the SCLC metastasis.

关 键 词：小细胞肺癌 WNT5A JNK 细胞迁移 

分 类 号：R734.2[医药卫生—肿瘤]