TY - JOUR
T1 - A novel nuclear localization region in SIPA1 determines protein nuclear distribution and epirubicin-sensitivity of breast cancer cells
AU - Ma, Ying
AU - Weng, Jun
AU - Wang, Ning
AU - Zhang, Yilei
AU - Minato, Nagahiro
AU - Su, Li
N1 - Funding Information:
The authors thank Dr. Peijing Zhang (Huazhong University of Science and Technology) for the great help in providing the breast cancer cell lines, and Dr. Yoshimasa Tanaka (Nagasaki University) for his great help in manuscript preparation, and the technical support from The Research Core Facilities for Life Science at College of Life Science and Technology, Huazhong University of Science and Technology. This work was supported by the grants from MOST - Key Program for International S&T Cooperation Projects of China (grant number 2017YFE0129100), China; and the National Natural Science Foundation of China (grant numbers 81872154, 31271504, and 31471310), China.
Funding Information:
This work was supported by the grants from MOST - Key Program for International S&T Cooperation Projects of China (grant number 2017YFE0129100 ), China; and the National Natural Science Foundation of China (grant numbers 81872154 , 31271504 , and 31471310 ), China.
Publisher Copyright:
© 2021 The Authors
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Signal-induced proliferation-associated protein 1 (SIPA1) is highly expressed and mainly located in the nucleus in some breast cancer cell lines and clinical tumor tissues. Previous study revealed that nuclear localization of SIPA1 is functionally involved in breast cancer metastasis in the lymphatic gland. In the current study, we identified a non-typical region (140-179aa) of SIPA1 as a novel nuclear localization region (NLR) which is crucial for translocating the proteins into the nucleus in HEK293 cells and breast cancer cells. This region contained one basic amino acid, His160, and had no common features of typical nuclear localization signals. In addition, overexpressing SIPA1 without NLR could suppress breast cancer cell proliferation but could not promote cell migration in MCF7 cells. Furthermore, we found that a high expression of SIPA1 upregulated the expression of ABCB1, encoding multi-drug resistance protein MDR1, and promoted the resistance to epirubicin in breast cancer cells, while this effect was largely abolished in the cells with the expression of NLR-deleted SIPA1. This study overall, identified a nuclear localization-dependent region determining the nuclear distribution of SIPA1 and its regulation on epirubicin-sensitivity in breast cancer cells, which could be a potential drug target to facilitate the development of breast cancer chemotherapy.
AB - Signal-induced proliferation-associated protein 1 (SIPA1) is highly expressed and mainly located in the nucleus in some breast cancer cell lines and clinical tumor tissues. Previous study revealed that nuclear localization of SIPA1 is functionally involved in breast cancer metastasis in the lymphatic gland. In the current study, we identified a non-typical region (140-179aa) of SIPA1 as a novel nuclear localization region (NLR) which is crucial for translocating the proteins into the nucleus in HEK293 cells and breast cancer cells. This region contained one basic amino acid, His160, and had no common features of typical nuclear localization signals. In addition, overexpressing SIPA1 without NLR could suppress breast cancer cell proliferation but could not promote cell migration in MCF7 cells. Furthermore, we found that a high expression of SIPA1 upregulated the expression of ABCB1, encoding multi-drug resistance protein MDR1, and promoted the resistance to epirubicin in breast cancer cells, while this effect was largely abolished in the cells with the expression of NLR-deleted SIPA1. This study overall, identified a nuclear localization-dependent region determining the nuclear distribution of SIPA1 and its regulation on epirubicin-sensitivity in breast cancer cells, which could be a potential drug target to facilitate the development of breast cancer chemotherapy.
KW - ABCB1
KW - Breast cancer
KW - Chemotherapy
KW - Nuclear localization
KW - SIPA1
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U2 - 10.1016/j.ijbiomac.2021.03.101
DO - 10.1016/j.ijbiomac.2021.03.101
M3 - Article
C2 - 33753200
AN - SCOPUS:85103083458
SN - 0141-8130
VL - 180
SP - 718
EP - 728
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -