NTF4 plays a dual role in breast cancer in mammary tumorigenesis and metastatic progression

作者全名："Sun, Ran; He, Jin; Xiang, Qin; Feng, Yixiao; Gong, Yijia; Ning, Yijiao; Deng, Chaoqun; Sun, Kexin; Zhang, Mingjun; Cheng, Zhaobo; Le, Xin; Xiong, Qi; Dai, Fengsheng; Wu, Yongzhong; Xiang, Tingxiu"

作者地址："[Sun, Ran; He, Jin; Xiang, Qin; Feng, Yixiao; Gong, Yijia; Ning, Yijiao; Deng, Chaoqun; Sun, Kexin; Le, Xin; Xiong, Qi; Dai, Fengsheng; Xiang, Tingxiu] Chongqing Med Univ, Affiliated Hosp 1, Dept Oncol, Chongqing 400016, Peoples R China; [Sun, Ran] Jiulongpo Peoples Hosp, Dept Oncol, Chongqing 400050, Peoples R China; [Zhang, Mingjun] Jiulongpo Peoples Hosp, Dept Lab Med, Chongqing 400050, Peoples R China; [Cheng, Zhaobo; Wu, Yongzhong; Xiang, Tingxiu] Chongqing Univ, Chongqing Key Lab Translat Res Canc Metastasis & I, Canc Hosp, Chongqing 400030, Peoples R China"

通信作者："Xiang, TX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Oncol, Chongqing 400016, Peoples R China.; Wu, YZ; Xiang, TX (通讯作者)，Chongqing Univ, Chongqing Key Lab Translat Res Canc Metastasis & I, Canc Hosp, Chongqing 400030, Peoples R China."

来源：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001018931900005

JCR分区：Q1

影响因子：8.2

年份：2023

卷号：19

期号：2

开始页：641

结束页：657

文献类型：Article

关键词：Breast cancer; NTF4; epithelial-mesenchymal transition; metastasis; apoptosis

摘要："Breast cancer metastasis can happen even when the primary tumor is relatively small. But the mechanism for such early metastasis is poorly understood. Herein, we report that neurotrophin 4 (NTF4) plays a dual role in breast cancer proliferation and metastasis. Clinical data showed high levels of NTF4, especially in the early stage, to be associated with poor clinical outcomes, supporting the notion that metastasis, rather than primary cancer, was the major determinant of breast cancer mortality for patients. NTF4 promoted epithelial-mesenchymal transition (EMT), cell motility, and invasiveness of breast cancer cells in vitro and in symbolscript Interestingly, NTF4 inhibited cell proliferation while promoting cellular apoptosis symbolscript symbolscript and inhibited xenograft tumorigenicity symbolscript symbolscript Mechanistically, NTF4 elicited its pro-metastatic effects by activating PRKDC/AKT and ANXA1/NF-& kappa;B pathways to stabilize SNAIL protein, therefore decreasing the level of E-cadherin. Conversely, NTF4 increased ANXA1 phosphorylation and sumoylation and the interaction with importin & beta;, leading to nuclear import and retention of ANXA1, which in turn activates the caspase-3 apoptosis cascade. Our findings identified an unexpected dual role for NTF4 in breast cancer which contributes to early metastasis of the disease. Therefore, NTF4 may serve as a prognostic marker and a potential therapeutic target for breast cancer."

基金机构："National Natural Science Foundation of China [82172619, 81872380]; Natural Science Foundation of Chongqing [cstc2019jcjy-msxmX0861, cstc2020jcyj-bshX0025, CSTC2021jscx-gksb-N0023]; Postdoctoral Science Foundation of China [2020M683262]; Postdoctoral Special Foundation of Chongqing [2021XM2011]"

基金资助正文："This study was supported by National Natural Science Foundation of China (#82172619, #81872380) , Natural Science Foundation of Chongqing (cstc2019jcjy-msxmX0861, cstc2020jcyj-bshX0025, CSTC2021jscx-gksb-N0023) , Postdoctoral Science Foundation of China (2020M683262) and Postdoctoral Special Foundation of Chongqing (2021XM2011) ."