AI Article Synopsis
- Transcription factors (TFs) control gene expression linked to cell growth and responses to the environment, and this study identified SIPA1 as a new TF that binds DNA.
- SIPA1 interacts with Importin β1 when cells are treated with fibronectin and regulates transcription of genes involved in key cellular processes like signal transduction and cell migration.
- The research showed that SIPA1 influences the transcription of fibronectin 1, important for the movement of triple-negative breast cancer cells, and its overexpression is observed in metastatic TNBC patient samples.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457189 | PMC |
| http://dx.doi.org/10.1038/s41388-023-02787-3 | DOI Listing |
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