Netrin-1 inducing antiapoptotic effect of acute myeloid leukemia cells in a concentration-dependent manner through the Unc-5 netrin receptor B-focal adhesion kinase axis

作者全名："Zhang, Kainan; An, Xizhou; Zhu, Yao; Huang, Lan; Yao, Xinyuan; Zeng, Xing; Liang, Shaoyan; Yu, Jie"

作者地址："[Zhang, Kainan; An, Xizhou; Zhu, Yao; Huang, Lan; Yao, Xinyuan; Zeng, Xing; Yu, Jie] Chongqing Med Univ, Childrens Hosp, Dept Hematol & Oncol, Chongqing, Peoples R China; [Zhang, Kainan; An, Xizhou; Zhu, Yao; Huang, Lan; Yao, Xinyuan; Zeng, Xing; Yu, Jie] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Zhang, Kainan; An, Xizhou; Zhu, Yao; Huang, Lan; Yao, Xinyuan; Zeng, Xing; Yu, Jie] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Zhang, Kainan; An, Xizhou; Zhu, Yao; Huang, Lan; Yao, Xinyuan; Zeng, Xing; Yu, Jie] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Zhang, Kainan; Zhu, Yao; Huang, Lan; Liang, Shaoyan] Chongqing Med Univ, Childrens Hosp, Pediat Res Inst, Chongqing, Peoples R China; [Yu, Jie] Chongqing Med Univ, Childrens Hosp, Dept Hematol & Oncol, 136 Zhongshanerlu, Chongqing 400014, Peoples R China"

通信作者："Yu, J (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Hematol & Oncol, 136 Zhongshanerlu, Chongqing 400014, Peoples R China."

来源：CANCER BIOLOGY & THERAPY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000965444100001

JCR分区：Q2

影响因子：3.6

年份：2023

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Netrin-1; acute myeloid leukemia; UNC5B; FAK-Akt; apoptosis

摘要："Acute myeloid leukemia (AML) is a hematological malignancy that commonly occurs in children. The prognosis of pediatric AML is relatively poor, thus threatening the patient's survival. The aberrant expression of the axon guidance factor, netrin-1, is observed in various types of malignancies, and it participates in the proliferation and apoptosis of tumor cells. Herein, we aimed to explore the role of netrin-1 in AML cells. Netrin-1 is highly expressed in AML patients. Proliferation and anti-apoptosis were observed in AML cells treated with netrin-1. The interaction between netrin-1 and Unc-5 netrin receptor B (UNC5B) was detected through coimmunoprecipitation, and UNC5B ribonucleic acid interference restrained the influence of netrin-1 on the AML cells. The phosphorylation of focal adhesion kinase-protein kinase B (FAK-Akt) was upregulated in AML cells treated with netrin-1. Both FAK and Akt inhibitors abrogated the effects of netrin-1 on the proliferation and apoptosis of AML cells. In conclusion, netrin-1 could promote the growth and reduce the apoptosis of AML cells in a concentration-dependent manner, and that these effects were mediated by activating the FAK-Akt signaling pathway via the UNC5B."

基金机构：National Natural Science Foundation of China [81700158]; Chongqing Science and Technology Commission Project [6000022]

基金资助正文：This research was supported by the National Natural Science Foundation of China (81700158) and Chongqing Science and Technology Commission Project (6000022)