Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.8
4.4
Journals
Cancers
Special Issues
PTEN: Regulation, Signalling and Targeting in Cancer
share announcement

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 2025 | Viewed by 22935

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 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

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

19 pages, 3360 KB  
Article
PTEN Inactivation in Mouse Colonic Epithelial Cells Curtails DSS-Induced Colitis and Accelerates Recovery
by Larissa Kotelevets, Francine Walker, Godefroy Mamadou, Bruno Eto, Thérèse Lehy and Eric Chastre
Cancers 2025, 17(14), 2346; https://doi.org/10.3390/cancers17142346 - 15 Jul 2025
Viewed by 635
Abstract
Background: PTEN is a tumor suppressor that controls many pathophysiological pathways, including cell proliferation, differentiation, apoptosis and invasiveness. Although PTEN down-modulation is a critical event in neoplastic progression, it becomes apparent that transient and local inhibition of PTEN activity might be beneficial [...] Read more.
Background: PTEN is a tumor suppressor that controls many pathophysiological pathways, including cell proliferation, differentiation, apoptosis and invasiveness. Although PTEN down-modulation is a critical event in neoplastic progression, it becomes apparent that transient and local inhibition of PTEN activity might be beneficial for the healing process. Methods: In the present study, we investigated the impact of PTEN invalidation in mouse intestinal epithelium under a physiological condition and after dextran sulfate sodium (DSS) treatment to induce experimental colitis. PTEN conditional knockout was induced in intestinal epithelial cells after crossing villin-Cre and PTENflox/flox mice. Results: PTEN invalidation alleviates experimental colitis induced by DSS, as evidenced by decreased weight loss during the acute phase, the lower expression of inflammation markers, including the proinflammatory cytokines IFN-γ, CXCL1 and CXCL2, reduced mucosal lesions, and faster recovery after resolution of inflammation. This protective effect might result in part from the sustained proliferation of colonic epithelium, leading to hyperplasia and increased colonic crypt depth under physiological conditions, which was further exacerbated in the vicinity of mucosal injury induced by DSS treatment. Furthermore, PTEN knockout decreased paracellular permeability, thereby enhancing the intestinal barrier function. This process was associated with the reinforcement of claudin-3 immunostaining, especially on the surface epithelium of villin-Cre PTENflox/flox mice. Conclusions: PTEN inactivation exerts a protective effect on the onset of colitis, and the transient and local down-modulation of PTEN might constitute an approach to drive recovery following acute intestinal inflammation. Full article
(This article belongs to the Special Issue PTEN: Regulation, Signalling and Targeting in Cancer)
►▼ Show Figures

Graphical abstract

13 pages, 3012 KB  
Article
Potentiation by Protein Synthesis Inducers of Translational Readthrough of Pathogenic Premature Termination Codons in PTEN Isoforms
by Leire Torices, Caroline E. Nunes-Xavier and Rafael Pulido
Cancers 2024, 16(16), 2836; https://doi.org/10.3390/cancers16162836 - 13 Aug 2024
Cited by 1 | Viewed by 1643
Abstract
The PTEN tumor suppressor is frequently targeted in tumors and patients with PTEN hamartoma tumor syndrome (PHTS) through nonsense mutations generating premature termination codons (PTC) that may cause the translation of truncated non-functional PTEN proteins. We have previously described a global analysis of [...] Read more.
The PTEN tumor suppressor is frequently targeted in tumors and patients with PTEN hamartoma tumor syndrome (PHTS) through nonsense mutations generating premature termination codons (PTC) that may cause the translation of truncated non-functional PTEN proteins. We have previously described a global analysis of the readthrough reconstitution of the protein translation and function of the human canonical PTEN isoform by aminoglycosides. Here, we report the efficient functional readthrough reconstitution of the PTEN translational isoform PTEN-L, which displays a minimal number of PTC in its specific N-terminal extension in association with disease. We illustrate the importance of the specific PTC and its nucleotide proximal sequence for optimal readthrough and show that the more frequent human PTEN PTC variants and their mouse PTEN PTC equivalents display similar patterns of readthrough efficiency. The heterogeneous readthrough response of the different PTEN PTC variants was independent of the length of the PTEN protein being reconstituted, and we found a correlation between the amount of PTEN protein being synthesized and the PTEN readthrough efficiency. Furthermore, combination of aminoglycosides and protein synthesis inducers increased the readthrough response of specific PTEN PTC. Our results provide insights with which to improve the functional reconstitution of human-disease-related PTC pathogenic variants from PTEN isoforms by increasing protein synthesis coupled to translational readthrough. Full article
(This article belongs to the Special Issue PTEN: Regulation, Signalling and Targeting in Cancer)
►▼ Show Figures

Figure 1

16 pages, 10608 KB  
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 5 | Viewed by 3920
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)
►▼ Show Figures

Figure 1

Review

Jump to: Research

19 pages, 743 KB  
Review
Drivers of Pancreatic Cancer: Beyond the Big 4
by Laura M. Porcza, Rafael Ballesteros-Cillero, Lok To Lam, Cristina Maiello and Nicholas R. Leslie
Cancers 2025, 17(14), 2354; https://doi.org/10.3390/cancers17142354 - 15 Jul 2025
Viewed by 1306
Abstract
Background: Pancreatic cancer is frequently identified as the cancer type with the shortest probable survival time after diagnosis, and efforts to develop successful treatments have had a very limited impact in the clinic. One reason for the limited therapeutic options is the lack [...] Read more.
Background: Pancreatic cancer is frequently identified as the cancer type with the shortest probable survival time after diagnosis, and efforts to develop successful treatments have had a very limited impact in the clinic. One reason for the limited therapeutic options is the lack of appealing drug targets. The great majority of pancreatic cancers are classified as Pancreatic Ductal Adenocarcinoma (PDAC), in which the genetic landscape is dominated by four genes: KRAS, TP53, CDKN2A, and SMAD4. However, despite extensive knowledge of these genetic drivers, the development of effective therapies has seen only very limited success. Methods: Existing evidence indicates that mutations in the tumour suppressor gene PTEN are uncommon in PDAC (<10% cases). However, the loss of PTEN function through non-genetic mechanisms may be much more common and have a strong impact. We therefore summarise and review a large body of immunohistochemical studies that address the loss of PTEN in PDAC as well as a smaller number of studies addressing other implicated proteins, including KDM6A and ARID1A. Results: These studies show some loss of PTEN protein in more than half of PDAC cases. Furthermore, although genetic changes in genes including KDM6A/UTX and ARID1A are also uncommon, reduced expression of their encoded proteins is observed in many, perhaps most, cases of PDAC. Conclusions: These analyses, which go beyond genetics, highlight the broader set of cellular functions that are dysregulated in many pancreatic cancers and provide broader opportunities for treatment strategies. This review highlights the emerging importance of other drivers in PDAC, which are less well-studied in this context. Full article
(This article belongs to the Special Issue PTEN: Regulation, Signalling and Targeting in Cancer)
►▼ Show Figures

Figure 1

20 pages, 1523 KB  
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 16 | Viewed by 3747
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)
►▼ Show Figures

Figure 1

15 pages, 1336 KB  
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 29 | Viewed by 3479
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)
►▼ Show Figures

Figure 1

22 pages, 3092 KB  
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 32 | Viewed by 5670
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)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop