ArticleMolecular oncology2015
TIPIN depletion leads to apoptosis in breast cancer cells.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
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- A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity.Cancers · 2021Review
- Predicting chemosensitivity using drug perturbed gene dynamics.BMC bioinformatics · 2021Article
- Construction of Gene Modules and Analysis of Prognostic Biomarkers for Cervical Cancer by Weighted Gene Co-Expression Network Analysis.Frontiers in oncology · 2021Article
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- A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.Nature communications · 2020Article
- Protein arginine methyltransferase 5: A novel therapeutic target for triple-negative breast cancers.Cancer medicine · 2019Article
- Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner.Nature communications · 2019Article
- Review
- LRP8 is overexpressed in estrogen-negative breast cancers and a potential target for these tumors.Cancer medicine · 2019Article
- LRP5 regulates the expression of STK40, a new potential target in triple-negative breast cancers.Oncotarget · 2018Article
- Cytidine Deaminase Deficiency Reveals New Therapeutic Opportunities against Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- TIPIN depletion leads to apoptosis in breast cancer cells.Molecular oncology · 2015Article
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is the breast cancer subgroup with the most aggressive clinical behavior. Alternatives to conventional chemotherapy are required to improve the survival of TNBC patients. Gene-expression analyses for different breast cancer subtypes revealed significant overexpression of the Timeless-interacting protein (TIPIN), which is involved in the stability of DNA replication forks, in the highly proliferative associated TNBC samples. Immunohistochemistry analysis showed higher expression of TIPIN in the most proliferative and aggressive breast cancer subtypes including TNBC, and no TIPIN expression in healthy breast tissues. The depletion of TIPIN by RNA interference impairs the proliferation of both human breast cancer and non-tumorigenic cell lines. However, this effect may be specifically associated with apoptosis in breast cancer cells. TIPIN silencing results in higher levels of single-stranded DNA (ssDNA), indicative of replicative stress (RS), in TNBC compared to non-tumorigenic cells. Upon TIPIN depletion, the speed of DNA replication fork was significantly decreased in all BC cells. However, TIPIN-depleted TNBC cells are unable to fire additional replication origins in response to RS and therefore undergo apoptosis. TIPIN knockdown in TNBC cells decreases tumorigenicity in vitro and delays tumor growth in vivo. Our findings suggest that TIPIN is important for the maintenance of DNA replication and represents a potential treatment target for the worst prognosis associated breast cancers, such as TNBC.
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