PTEN in the maintenance of genome integrity: From DNA replication to chromosome segregation
Open accessAbstract
Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment.
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PTEN is involved in maintaining mitotic spindle architecture and promoting chromosome alignment and segregation.
“PTEN is involved in maintaining mitotic spindle architecture and promoting chromosome alignment and segregation, functions overlapping with the postulated mechanism of action of TTFields [8,91,92].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [91]
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Johnson, A. M., Jose, S., Palakkott, A. R., Khan, F. B., Jayabalan, N., Kizhakkayil, J., AlNaqbi, S. A. A., Scott, M. G. H., Ayoub, M. A., Gordon, R., et al. (2023) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-023-10077-8 · Cited by 6 · see citing works
Looking closely at overgrowth: Constitutional mosaicism in PTEN hamartoma tumor syndrome
Newman, H. M., Long, J. M., Zelley, K., Baldino, S. E., Li, M. M., Maxwell, K. N., & MacFarland, S. P. (2022) · Clinical Genetics · doi:10.1111/cge.14202 · Cited by 5 · see citing works
Mukherjee, A., Vankamamidi, S. E., & Mukunthan, K. S. (2025) · Scientific Reports · doi:10.1038/s41598-025-11473-1 · Cited by 4 · see citing works
Wei, R., Hitomi, M., Sadler, T. M., Yehia, L., Daniela Calvetti, A., Scott, J. G., & Eng, C. (2024) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1012449 · Cited by 4 · see citing works
Defining the Molecular Intricacies of Human Papillomavirus-Associated Tonsillar Carcinoma
Sethi, S. (2025) · Cancer Control: Journal of the Moffitt Cancer Cente · doi:10.1177/10732748241310932 · Cited by 3 · see citing works
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NHEJ is promoted by the phosphorylation and phosphatase activity of PTEN via regulation of DNA-PKcs
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Crosstalk Between Plk1 and PTEN in Mitosis Affects Chromosomal Stability
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Autophagy in Ovarian Cancer, an Opportunity or an Additional Threat?
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PTEN mutant NSCLC require ATM to suppress pro-apoptotic signalling and evade radiotherapyPreprint
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PTEN: Sumoylation Function is the Key to the Maintenance of Genomic Stability of Cell
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PTEN regulates actin filaments to shape cell cortex architecturePreprint
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PTEN: Redefining tumor suppressor functions in cancer by regulating transcription.
Hameed, J. S. F., Chowdhury, S. G., Karmakar, P., Ganesan, T., & Mukherjee, A. (2026) · Biochimica et biophysica acta. Reviews on cancer · doi:10.1016/j.bbcan.2026.189659
- Authors
- Hou, S., Ouyang, M., Brandmaier, A., Hao, H., & Shen, W. H.
- Affiliations
- Department of Radiation Oncology, Weill Cornell Medicine Cornell University New York NY USA
- Cornell University (US)
- Corresponding author
- Shen, Wen H.
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2017-09-11
- Volume
- 39
- Issue
- 10
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- PMC
- PMC5659364
- OpenAlex
- W2754301172
- Cited by
- 65
- References
- 51
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 14 · 2019: 7 · 2018: 8
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- BioEssays (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Irma T. Hirschl Trust
- National Institute of General Medical Sciences (R01GM100478)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- PTEN, genome stability, DNA replication, chromosome segregation, tumor suppressor, genomic instability, aneuploidy, replication stress, mitotic spindle, chromosomal instability, cancer therapy targets
- MeSH terms
- Animals, DNA Replication, Humans, Spindle Apparatus, Chromosome Segregation, Genomic Instability, Chromosomal Instability, PTEN Phosphohydrolase
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