Non-genomic loss of PTEN function in cancer: not in my genes
Nick R Leslie1, Michelangelo Foti
1Division of Molecular Physiology, College of Life Sciences, University of Dundee, Wellcome Trust Biocentre, Dow Street, Dundee DD1 5EH, UK. n.r.leslie@dundee.ac.uk
Abstract:
Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice with reductions in PTEN gene dosage indicate that even partial loss of PTEN function is sufficient to promote some cancer types, particularly in the breast. PTEN expression appears to be tightly controlled both transcriptionally and post-transcriptionally, with several recent studies implicating oncogenic microRNAs in PTEN suppression. The lipid phosphatase activity of PTEN can also be regulated post-translationally via inhibitory phosphorylation, ubiquitination or oxidation. Here we discuss these multiple mechanisms of PTEN regulation. We also put into context recent proposals that changes in this regulation can drive tumour development and address the accompanying evidence for their clinical significance.
Insights
Partial loss of phosphatase and tensin homolog (PTEN) tumor suppressor function promotes cancer, especially breast cancer. PTEN regulation is complex, involving transcriptional, post-transcriptional, and post-translational mechanisms that impact tumor development and clinical significance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Loss of function of the phosphatase and tensin homolog (PTEN) tumor suppressor is implicated in numerous cancers.
- Partial loss of PTEN function, rather than complete loss, is frequently observed in clinical settings.
- Reduced PTEN gene dosage in humans and mice promotes certain cancer types, notably breast cancer.
Purpose of the Study:
- To discuss the multiple regulatory mechanisms of PTEN.
- To contextualize how PTEN dysregulation drives tumor development.
- To address the clinical significance of PTEN alterations in cancer.
Main Methods:
- Review of existing literature on PTEN regulation.
- Analysis of studies investigating PTEN gene dosage effects.
- Discussion of transcriptional, post-transcriptional, and post-translational control of PTEN.
Main Results:
- PTEN expression is tightly controlled through various mechanisms.
- Oncogenic microRNAs are implicated in PTEN suppression.
- Post-translational modifications like phosphorylation, ubiquitination, and oxidation regulate PTEN activity.
Conclusions:
- Dysregulation of PTEN, even partial loss of function, significantly contributes to cancer development.
- Understanding PTEN regulation is crucial for evaluating its clinical significance in oncology.
- Multiple layers of PTEN control offer potential therapeutic targets in cancer treatment.
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