Int J Biol Sci 2023; 19(2):641-657. doi:10.7150/ijbs.79435 This issue Cite

Research Paper

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

Ran Sun1,2#, Jin He1#, Qin Xiang1#, Yixiao Feng1, Yijia Gong1, Yijiao Ning1, Chaoqun Deng1, Kexin Sun1, Mingjun Zhang3, Zhaobo Cheng4, Xin Le1, Qi Xiong1, Fengsheng Dai1, Yongzhong Wu4✉, Tingxiu Xiang1,4✉

1. Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
2. Department of Oncology, Jiulongpo People's Hospital, Chongqing 400050, China.
3. Department of Laboratory Medicine, Jiulongpo People's Hospital, Chongqing 400050, China.
4. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China.
#These authors have contributed equally to this work.

Citation:
Sun R, He J, Xiang Q, Feng Y, Gong Y, Ning Y, Deng C, Sun K, Zhang M, Cheng Z, Le X, Xiong Q, Dai F, Wu Y, Xiang T. NTF4 plays a dual role in breast cancer in mammary tumorigenesis and metastatic progression. Int J Biol Sci 2023; 19(2):641-657. doi:10.7150/ijbs.79435. https://www.ijbs.com/v19p0641.htm
Other styles

File import instruction

Abstract

Graphic abstract

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 vivo. Interestingly, NTF4 inhibited cell proliferation while promoting cellular apoptosis in vitro and inhibited xenograft tumorigenicity in vivo. Mechanistically, NTF4 elicited its pro-metastatic effects by activating PRKDC/AKT and ANXA1/NF-κB pathways to stabilize SNAIL protein, therefore decreasing the level of E-cadherin. Conversely, NTF4 increased ANXA1 phosphorylation and sumoylation and the interaction with importin β, 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.

Keywords: Breast cancer, NTF4, epithelial-mesenchymal transition, metastasis, apoptosis


Citation styles

APA
Sun, R., He, J., Xiang, Q., Feng, Y., Gong, Y., Ning, Y., Deng, C., Sun, K., Zhang, M., Cheng, Z., Le, X., Xiong, Q., Dai, F., Wu, Y., Xiang, T. (2023). NTF4 plays a dual role in breast cancer in mammary tumorigenesis and metastatic progression. International Journal of Biological Sciences, 19(2), 641-657. https://doi.org/10.7150/ijbs.79435.

ACS
Sun, R.; He, J.; Xiang, Q.; Feng, Y.; Gong, Y.; Ning, Y.; Deng, C.; Sun, K.; Zhang, M.; Cheng, Z.; Le, X.; Xiong, Q.; Dai, F.; Wu, Y.; Xiang, T. NTF4 plays a dual role in breast cancer in mammary tumorigenesis and metastatic progression. Int. J. Biol. Sci. 2023, 19 (2), 641-657. DOI: 10.7150/ijbs.79435.

NLM
Sun R, He J, Xiang Q, Feng Y, Gong Y, Ning Y, Deng C, Sun K, Zhang M, Cheng Z, Le X, Xiong Q, Dai F, Wu Y, Xiang T. NTF4 plays a dual role in breast cancer in mammary tumorigenesis and metastatic progression. Int J Biol Sci 2023; 19(2):641-657. doi:10.7150/ijbs.79435. https://www.ijbs.com/v19p0641.htm

CSE
Sun R, He J, Xiang Q, Feng Y, Gong Y, Ning Y, Deng C, Sun K, Zhang M, Cheng Z, Le X, Xiong Q, Dai F, Wu Y, Xiang T. 2023. NTF4 plays a dual role in breast cancer in mammary tumorigenesis and metastatic progression. Int J Biol Sci. 19(2):641-657.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image