A novel nuclear localization region in SIPA1 determines protein nuclear distribution and epirubicin-sensitivity of breast cancer cells
A novel nuclear localization region in SIPA1 determines protein nuclear distribution and epirubicin-sensitivity of breast cancer cells
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SIPA1 中的一个新核定位区域决定乳腺癌细胞的蛋白质核分布和表阿霉素敏感性
DOI：
10.1016/j.ijbiomac.2021.03.101
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发表时间：
2021-03-25
影响因子：
8.2
通讯作者：
Su, Li
中科院分区：
文献类型：
--
作者：
Ma, Ying;Weng, Jun;Su, Li
信号诱导增殖相关蛋白1（Signal-induced proliferation-associated protein 1，SIPA 1）在一些乳腺癌细胞系和临床肿瘤组织中高度表达，主要定位于细胞核。以往的研究表明，SIPA 1的核定位在功能上参与了乳腺癌淋巴结转移。在目前的研究中，我们确定了SIPA 1的非典型区域（140- 179 aa）作为一个新的核定位区（NLR），这是至关重要的蛋白质易位到细胞核中的HEK 293细胞和乳腺癌细胞。该区域含有一个碱性氨基酸His 160，没有典型核定位信号的共同特征。此外，在没有NLR的情况下过表达SIPA 1可以抑制乳腺癌细胞增殖，但不能促进MCF 7细胞的细胞迁移。此外，我们发现SIPA 1的高表达上调了ABCB 1的表达，编码多药耐药蛋白MDR 1，并促进乳腺癌细胞对表阿霉素的耐药性，而这种作用在表达NLR缺失的SIPA 1的细胞中基本上被消除。这项研究总体上确定了一个核定位依赖性区域，该区域决定了SIPA 1的核分布及其对乳腺癌细胞表柔比星敏感性的调节，这可能是促进乳腺癌化疗发展的潜在药物靶点。(c)2021作者由爱思唯尔公司出版。这是一篇开放获取的文章，使用CC BY许可证（http：//creativecommons.org/licenses/by/4.0/）。
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.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).