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白细胞介素-13受体α2是人类肺癌的一个负性预后因素,并能促进小鼠肺癌生长。

IL-13 receptor α2 is a negative prognostic factor in human lung cancer and stimulates lung cancer growth in mice.

作者信息

Xie Mian, Wu Xiao-jun, Zhang Jin-jun, He Chao-sheng

机构信息

China State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

State Key Laboratory of Oncology in Southern China, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Oncotarget. 2015 Oct 20;6(32):32902-13. doi: 10.18632/oncotarget.5361.

Abstract

IL-13 receptor subunit alpha-2 (IL13Rα2) is associated with poor prognosis in some cancers. However, the role of IL13Rα2 in lung cancer remains unknown. We showed that IL13Rα2 overexpression was associated with late stages of disease progression and shorter disease-free survival (DFS) as well as overall survival (OS) in resected lung cancer patients. IL13Rα2 promoted the migration, invasion and anoikis resistance of lung cancer cells in vitro. Silencing of IL13Rα2 in lung cancer cells decreased invasion in vitro and lung metastasis in vivo. IL13Rα2 activated phosphatidylinositol 3 kinase (PI3K), Akt, and transcriptional coactivator with PDZ-binding motif (TAZ). Inhibition of PI3K attenuated activation of TAZ and its downstream target genes by IL13Rα2. We suggest that inhibition of IL13Rα2 is a potential therapeutic approach in lung cancer.

摘要

白细胞介素-13受体α2亚基(IL13Rα2)与某些癌症的不良预后相关。然而,IL13Rα2在肺癌中的作用仍不清楚。我们发现,IL13Rα2过表达与接受手术切除的肺癌患者的疾病进展晚期、较短的无病生存期(DFS)以及总生存期(OS)相关。IL13Rα2在体外促进肺癌细胞的迁移、侵袭和失巢凋亡抗性。肺癌细胞中IL13Rα2的沉默降低了体外侵袭和体内肺转移。IL13Rα2激活磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)以及含PDZ结合基序的转录共激活因子(TAZ)。PI3K的抑制减弱了IL13Rα2对TAZ及其下游靶基因的激活作用。我们认为,抑制IL13Rα2是肺癌的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/945d/4741738/e9342891ce6b/oncotarget-06-32902-g001.jpg

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