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一个新的转录因子 SIPA1：在三阴性乳腺癌中的鉴定和验证。

A novel transcription factor SIPA1: identification and verification in triple-negative breast cancer.

机构信息

Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

Department of Breast Surgery, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China.

出版信息

Oncogene. 2023 Aug;42(35):2641-2654. doi: 10.1038/s41388-023-02787-3. Epub 2023 Jul 27.

DOI:10.1038/s41388-023-02787-3
PMID:37500797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10457189/
Abstract

Transcription factors (TFs) regulate the expression of genes responsible for cell growth, differentiation, and responses to environmental factors. In this study, we demonstrated that signal-induced proliferation-associated 1 (SIPA1), known as a Rap-GTPase-activating protein, bound DNA and served as a TF. Importin β1 was found to interact with SIPA1 upon fibronectin treatment. A TGAGTCAB motif was recognized and bound by DNA-binding region (DBR) of SIPA1, which was confirmed by electrophoretic mobility shift assay. SIPA1 regulated the transcription of multiple genes responsible for signal transduction, DNA synthesis, cell adhesion, cell migration, and so on. Transcription of fibronectin 1, which is crucial for cell junction and migration of triple-negative breast cancer (TNBC) cells, was regulated by SIPA1 in a DBR-dependent manner both in vivo and in vitro. Furthermore, single-cell transcriptome sequencing analysis of specimens from a metastatic TNBC patient revealed that SIPA1 was highly expressed in metastatic TNBC. Hence, this study demonstrated that SIPA1 served as a TF, promoting TNBC migration, invasion, and metastasis.

摘要

转录因子 (TFs) 调节负责细胞生长、分化和对环境因素反应的基因的表达。在这项研究中，我们证明了信号诱导增殖相关蛋白 1 (SIPA1)，作为一种 Rap-GTPase 激活蛋白，结合 DNA 并充当 TF。发现纤维连接蛋白处理后，Importin β1 与 SIPA1 相互作用。通过电泳迁移率变动分析证实，SIPA1 的 DNA 结合区域 (DBR) 识别并结合 TGAGTCAB 基序。SIPA1 调节多个信号转导、DNA 合成、细胞黏附、细胞迁移等相关基因的转录。纤维连接蛋白 1 的转录对于三阴性乳腺癌 (TNBC) 细胞的细胞连接和迁移至关重要，SIPA1 通过 DBR 依赖性方式在体内和体外均调节其转录。此外，对转移性 TNBC 患者标本的单细胞转录组测序分析显示，SIPA1 在转移性 TNBC 中高度表达。因此，本研究表明 SIPA1 作为 TF 促进了 TNBC 的迁移、侵袭和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/ced9937a89a5/41388_2023_2787_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/4d99527c546c/41388_2023_2787_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/58d9b71c2f52/41388_2023_2787_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/0cfaa9c8b19b/41388_2023_2787_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/d32b4b42fdb1/41388_2023_2787_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/6d79b5bfaee2/41388_2023_2787_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/dc46a0dbcf63/41388_2023_2787_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/ced9937a89a5/41388_2023_2787_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/4d99527c546c/41388_2023_2787_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/58d9b71c2f52/41388_2023_2787_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/0cfaa9c8b19b/41388_2023_2787_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/d32b4b42fdb1/41388_2023_2787_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/6d79b5bfaee2/41388_2023_2787_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/dc46a0dbcf63/41388_2023_2787_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e112/10457189/ced9937a89a5/41388_2023_2787_Fig7_HTML.jpg

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