The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation
Open accessAbstract
The splicing-factor oncoprotein SRSF1 (also known as SF2/ASF or ASF/SF2) is upregulated in breast cancers. We investigated the ability of SRSF1 to transform human and mouse mammary epithelial cells in vivo and in vitro. SRSF1-overexpressing COMMA-1D cells formed tumors, following orthotopic transplantation to reconstitute the mammary gland. In three-dimensional (3D) culture, SRSF1-overexpressing MCF-10A cells formed larger acini than control cells, reflecting increased proliferation and delayed apoptosis during acinar morphogenesis. These effects required the first RNA-recognition motif and nuclear functions of SRSF1. SRSF1 overexpression promoted alternative splicing of BIM (also known as BCL2L11) and BIN1 to produce isoforms that lack pro-apoptotic functions and contribute to the phenotype. Finally, SRSF1 cooperated specifically with MYC to transform mammary epithelial cells, in part by potentiating eIF4E activation, and these cooperating oncogenes are significantly coexpressed in human breast tumors. Thus, SRSF1 can promote breast cancer, and SRSF1 itself or its downstream effectors may be valuable targets for the development of therapeutics.
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Cites
Alternative isoform regulation in human tissue transcriptomes
Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., & Burge, C. B. (2008) · Nature · doi:10.1038/nature07509 · Cited by 5,181
Listening to silence and understanding nonsense: exonic mutations that affect splicing
Cartegni, L., Chew, S. L., & Krainer, A. R. (2002) · Nature Reviews Genetics · doi:10.1038/nrg775 · Cited by 2,209
Self-citationSpecific protection against breast cancers by cyclin D1 ablation
Yu, Q., Geng, Y., & Sicinski, P. (2001) · Nature · doi:10.1038/35082500 · Cited by 934
Zhan, L., Rosenberg, A., Bergami, K. C., Yu, M., Xuan, Z., Jaffe, A. B., Allred, C., & Muthuswamy, S. K. (2008) · Cell · doi:10.1016/j.cell.2008.09.045 · Cited by 436
Self-citationBIN1 is a novel MYC–interacting protein with features of a tumour suppressor
Sakamuro, D., Elliott, K. J., Wechsler-Reya, R., & Prendergast, G. C. (1996) · Nature Genetics · doi:10.1038/ng0996-69 · Cited by 387
Cited by
RNA-Binding Proteins in Cancer: Old Players and New Actors
Pereira, B., Billaud, M., & Almeida, R. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.05.003 · Cited by 773
RNA splicing dysregulation and the hallmarks of cancer
Bradley, R. K., & Anczuków, O. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00541-7 · Cited by 579
Self-citationTherapeutic targeting of splicing in cancer
Lee, S. C.-W., & Abdel-Wahab, O. (2016) · Nature Medicine · doi:10.1038/nm.4165 · Cited by 561
MYC: Connecting selective transcriptional control to global RNA production
Kress, T. R., Sabò, A., & Amati, B. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3984 · Cited by 521
Nuclear speckles: molecular organization, biological function and role in disease
Galganski, L., Urbanek, M. O., & Krzyzosiak, W. J. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx759 · Cited by 499
Metadata
- Authors
- Anczuków, O., Rosenberg, A. Z., Akerman, M., Das, S., Zhan, L., Karni, R., Muthuswamy, S. K., & Krainer, A. R.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2012-01-15
- Volume
- 19
- Issue
- 2
- Pages
- 220-228
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2000567082
- Cited by
- 447
- References
- 5
- FWCI
- 11.38
- Type
- journal article
- Language
- en
- Open access
- green
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- Anczuków, O., Rosenberg, A. Z., Akerman, M., Das, S., Zhan, L., Karni, R., Muthuswamy, S. K., & Krainer, A. R. (2012). The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.2207
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