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Cancers
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PTEN: Regulation, Signalling and Targeting in Cancer
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PTEN: Regulation, Signalling and Targeting in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 10310

Special Issue Editors

Dr. Mark G.H. Scott

E-Mail Website
Guest Editor
Institut Cochin, CNRS UMR8104, INSERM U1016, Université de Paris, 75014 Paris, France
Interests: PTEN; PI3-kinase; Akt; cell signalling; molecular scaffolds; biosensors
Dr. Larissa Kotelevets

E-Mail Website
Guest Editor
Sorbonne Université, INSERM, UMR_S938, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France
Interests: PTEN; PI3-kinase; molecular scaffolds; junctional complexes; E-cadherin; mouse models of cancer
Dr. Éric Chastre

E-Mail Website
Guest Editor
Centre de Recherche Saint-Antoine (CRSA), INSERM UMR_S938, 75012 Paris, France
Interests: PTEN; PI3-kinase; Akt; cell signalling; colorectal cancer; mouse models of cancer

Special Issue Information

Dear Colleagues,

PTEN is a tumour suppressor with frequent loss-of-function events documented in sporadic and heritable cancers. It dephosphorylates protein substrates, but also the lipid signalling intermediate PIP3, generated by PI3K, curtailing the Akt pathway. Additionally, PTEN exerts functions independently of its phosphatase activity, via scaffolding partner proteins to form signalosomes. These pleiotropic functions of PTEN enable it to control key biological processes involved in carcinogenesis, including cell proliferation, differentiation, migration and apoptosis. PTEN levels and activity are subjected to fine-tuning, through epigenetic mechanisms, transcription, RNA stability, post-translational modifications, protein–protein interactions and subcellular targeting, which are all susceptible to alteration during carcinogenesis.

We are pleased to invite authors to submit their original or review articles to this Special Issue entitled “PTEN: Regulation, Signalling and Targeting in Cancer". Articles focused on PTEN signalling and (dys)regulation, molecular partners, effector systems and their pathophysiological significance will be considered. Translational studies aimed at monitoring, restoring or substituting PTEN function also fall within the scope of this Special Issue.

This Special Issue aims to provide a resource for researchers interested in: i) different levels of PTEN regulation and function, and the underlying mechanisms/biological impact associated with its dysregulation during carcinogenesis; and ii) in the definition of biomarkers with prognostic value and/or putative targets for precision medicine. We look forward to receiving your contributions.

Dr. Mark G.H. Scott
Dr. Larissa Kotelevets
Dr. Éric Chastre
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • PTEN
  • tumour suppressor
  • phosphatase
  • AKT signalling
  • genome integrity
  • apoptosis
  • proliferation
  • cancer
  • biomarker
  • precision medicine

Published Papers (4 papers)

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Research

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16 pages, 10608 KiB  
Article
FABP5 Inhibition against PTEN-Mutant Therapy Resistant Prostate Cancer
by Manojit M. Swamynathan, Grinu Mathew, Andrei Aziz, Chris Gordon, Andrew Hillowe, Hehe Wang, Aashna Jhaveri, Jude Kendall, Hilary Cox, Michael Giarrizzo, Gissou Azabdaftari, Robert C. Rizzo, Sarah D. Diermeier, Iwao Ojima, Agnieszka B. Bialkowska, Martin Kaczocha and Lloyd C. Trotman
Cancers 2024, 16(1), 60; https://doi.org/10.3390/cancers16010060 - 21 Dec 2023
Cited by 2 | Viewed by 1668
Abstract
Resistance to standard of care taxane and androgen deprivation therapy (ADT) causes the vast majority of prostate cancer (PC) deaths worldwide. We have developed RapidCaP, an autochthonous genetically engineered mouse model of PC. It is driven by the loss of PTEN and p53, [...] Read more.
Resistance to standard of care taxane and androgen deprivation therapy (ADT) causes the vast majority of prostate cancer (PC) deaths worldwide. We have developed RapidCaP, an autochthonous genetically engineered mouse model of PC. It is driven by the loss of PTEN and p53, the most common driver events in PC patients with life-threatening diseases. As in human ADT, surgical castration of RapidCaP animals invariably results in disease relapse and death from the metastatic disease burden. Fatty Acid Binding Proteins (FABPs) are a large family of signaling lipid carriers. They have been suggested as drivers of multiple cancer types. Here we combine analysis of primary cancer cells from RapidCaP (RCaP cells) with large-scale patient datasets to show that among the 10 FABP paralogs, FABP5 is the PC-relevant target. Next, we show that RCaP cells are uniquely insensitive to both ADT and taxane treatment compared to a panel of human PC cell lines. Yet, they share an exquisite sensitivity to the small-molecule FABP5 inhibitor SBFI-103. We show that SBFI-103 is well tolerated and can strongly eliminate RCaP tumor cells in vivo. This provides a pre-clinical platform to fight incurable PC and suggests an important role for FABP5 in PTEN-deficient PC. Full article
(This article belongs to the Special Issue PTEN: Regulation, Signalling and Targeting in Cancer)
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Review

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20 pages, 1523 KiB  
Review
PTEN, PTENP1, microRNAs, and ceRNA Networks: Precision Targeting in Cancer Therapeutics
by Glena Travis, Eileen M. McGowan, Ann M. Simpson, Deborah J. Marsh and Najah T. Nassif
Cancers 2023, 15(20), 4954; https://doi.org/10.3390/cancers15204954 - 12 Oct 2023
Cited by 2 | Viewed by 1478
Abstract
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental cellular processes including cell proliferation, migration, metabolism, and survival. Subtle decreases in cellular levels of PTEN [...] Read more.
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental cellular processes including cell proliferation, migration, metabolism, and survival. Subtle decreases in cellular levels of PTEN result in the development and progression of cancer, hence there is tight regulation of the expression, activity, and cellular half-life of PTEN at the transcriptional, post-transcriptional, and post-translational levels. PTENP1, the processed pseudogene of PTEN, is an important transcriptional and post-transcriptional regulator of PTEN. PTENP1 expression produces sense and antisense transcripts modulating PTEN expression, in conjunction with miRNAs. Due to the high sequence similarity between PTEN and the PTENP1 sense transcript, the transcripts possess common miRNA binding sites with the potential for PTENP1 to compete for the binding, or ‘sponging’, of miRNAs that would otherwise target the PTEN transcript. PTENP1 therefore acts as a competitive endogenous RNA (ceRNA), competing with PTEN for the binding of specific miRNAs to alter the abundance of PTEN. Transcription from the antisense strand produces two functionally independent isoforms (PTENP1-AS-α and PTENP1-AS-β), which can regulate PTEN transcription. In this review, we provide an overview of the post-transcriptional regulation of PTEN through interaction with its pseudogene, the cellular miRNA milieu and operation of the ceRNA network. Furthermore, its importance in maintaining cellular integrity and how disruption of this PTEN–miRNA–PTENP1 axis may lead to cancer but also provide novel therapeutic opportunities, is discussed. Precision targeting of PTENP1-miRNA mediated regulation of PTEN may present as a viable alternative therapy. Full article
(This article belongs to the Special Issue PTEN: Regulation, Signalling and Targeting in Cancer)
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15 pages, 1336 KiB  
Review
Targeting PTEN Regulation by Post Translational Modifications
by Ana González-García, Antonio Garrido and Ana C. Carrera
Cancers 2022, 14(22), 5613; https://doi.org/10.3390/cancers14225613 - 15 Nov 2022
Cited by 10 | Viewed by 1924
Abstract
Phosphatidylinositol-3,4,5-triphosphate (PIP3) is a lipidic second messenger present at very low concentrations in resting normal cells. PIP3 levels, though, increase quickly and transiently after growth factor addition, upon activation of phosphatidylinositol 3-kinase (PI3-kinase). PIP3 is required for the activation [...] Read more.
Phosphatidylinositol-3,4,5-triphosphate (PIP3) is a lipidic second messenger present at very low concentrations in resting normal cells. PIP3 levels, though, increase quickly and transiently after growth factor addition, upon activation of phosphatidylinositol 3-kinase (PI3-kinase). PIP3 is required for the activation of intracellular signaling pathways that induce cell proliferation, cell migration, and survival. Given the critical role of this second messenger for cellular responses, PIP3 levels must be tightly regulated. The lipid phosphatase PTEN (phosphatase and tensin-homolog in chromosome 10) is the phosphatase responsible for PIP3 dephosphorylation to PIP2. PTEN tumor suppressor is frequently inactivated in endometrium and prostate carcinomas, and also in glioblastoma, illustrating the contribution of elevated PIP3 levels for cancer development. PTEN biological activity can be modulated by heterozygous gene loss, gene mutation, and epigenetic or transcriptional alterations. In addition, PTEN can also be regulated by post-translational modifications. Acetylation, oxidation, phosphorylation, sumoylation, and ubiquitination can alter PTEN stability, cellular localization, or activity, highlighting the complexity of PTEN regulation. While current strategies to treat tumors exhibiting a deregulated PI3-kinase/PTEN axis have focused on PI3-kinase inhibition, a better understanding of PTEN post-translational modifications could provide new therapeutic strategies to restore PTEN action in PIP3-dependent tumors. Full article
(This article belongs to the Special Issue PTEN: Regulation, Signalling and Targeting in Cancer)
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22 pages, 3092 KiB  
Review
The Role of PTEN in Epithelial–Mesenchymal Transition
by Olga Fedorova, Sergey Parfenyev, Alexandra Daks, Oleg Shuvalov and Nickolai A. Barlev
Cancers 2022, 14(15), 3786; https://doi.org/10.3390/cancers14153786 - 3 Aug 2022
Cited by 12 | Viewed by 3934
Abstract
Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN) is one of the critical tumor suppressor genes and the main negative regulator of the PI3K pathway. PTEN is frequently found to be inactivated, either partially or fully, in various malignancies. The PI3K/AKT pathway [...] Read more.
Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN) is one of the critical tumor suppressor genes and the main negative regulator of the PI3K pathway. PTEN is frequently found to be inactivated, either partially or fully, in various malignancies. The PI3K/AKT pathway is considered to be one of the main signaling cues that drives the proliferation of cells. Perhaps it is not surprising, then, that this pathway is hyperactivated in highly proliferative tumors. Importantly, the PI3K/AKT pathway also coordinates the epithelial–mesenchymal transition (EMT), which is pivotal for the initiation of metastases and hence is regarded as an attractive target for the treatment of metastatic cancer. It was shown that PTEN suppresses EMT, although the exact mechanism of this effect is still not fully understood. This review is an attempt to systematize the published information on the role of PTEN in the development of malignant tumors, with a main focus on the regulation of the PI3K/AKT pathway in EMT. Full article
(This article belongs to the Special Issue PTEN: Regulation, Signalling and Targeting in Cancer)
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