PTEN Tumor-Suppressor: The Dam of Stemness in Cancer
<i>PTEN</i> is one of the most frequently inactivated tumor suppressor genes in cancer. Loss or variation in <i>PTEN</i> gene/protein levels is commonly observed in a broad spectrum of human cancers, while germline <i>PTEN</i> mutations cause inherited syndromes t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/8/1076 |
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| author | Francesca Luongo Francesca Colonna Federica Calapà Sara Vitale Micol E. Fiori Ruggero De Maria |
| author_facet | Francesca Luongo Francesca Colonna Federica Calapà Sara Vitale Micol E. Fiori Ruggero De Maria |
| author_sort | Francesca Luongo |
| collection | DOAJ |
| description | <i>PTEN</i> is one of the most frequently inactivated tumor suppressor genes in cancer. Loss or variation in <i>PTEN</i> gene/protein levels is commonly observed in a broad spectrum of human cancers, while germline <i>PTEN</i> mutations cause inherited syndromes that lead to increased risk of tumors. <i>PTEN</i> restrains tumorigenesis through different mechanisms ranging from phosphatase-dependent and independent activities, subcellular localization and protein interaction, modulating a broad array of cellular functions including growth, proliferation, survival, DNA repair, and cell motility. The main target of <i>PTEN</i> phosphatase activity is one of the most significant cell growth and pro-survival signaling pathway in cancer: PI3K/AKT/mTOR. Several shreds of evidence shed light on the critical role of <i>PTEN</i> in normal and cancer stem cells (CSCs) homeostasis, with its loss fostering the CSC compartment in both solid and hematologic malignancies. CSCs are responsible for tumor propagation, metastatic spread, resistance to therapy, and relapse. Thus, understanding how alterations of <i>PTEN</i> levels affect CSC hallmarks could be crucial for the development of successful therapeutic approaches. Here, we discuss the most significant findings on <i>PTEN</i>-mediated control of CSC state. We aim to unravel the role of <i>PTEN</i> in the regulation of key mechanisms specific for CSCs, such as self-renewal, quiescence/cell cycle, Epithelial-to-Mesenchymal-Transition (EMT), with a particular focus on <i>PTEN</i>-based therapy resistance mechanisms and their exploitation for novel therapeutic approaches in cancer treatment. |
| first_indexed | 2024-03-12T06:27:29Z |
| format | Article |
| id | doaj.art-dafff1cbf36044dcb85e9742a83107c0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:27:29Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dafff1cbf36044dcb85e9742a83107c02023-09-03T01:51:18ZengMDPI AGCancers2072-66942019-07-01118107610.3390/cancers11081076cancers11081076PTEN Tumor-Suppressor: The Dam of Stemness in CancerFrancesca Luongo0Francesca Colonna1Federica Calapà2Sara Vitale3Micol E. Fiori4Ruggero De Maria5Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, ItalyIstituto di Patologia Generale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, ItalyIstituto di Patologia Generale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, ItalyIstituto di Patologia Generale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyIstituto di Patologia Generale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy<i>PTEN</i> is one of the most frequently inactivated tumor suppressor genes in cancer. Loss or variation in <i>PTEN</i> gene/protein levels is commonly observed in a broad spectrum of human cancers, while germline <i>PTEN</i> mutations cause inherited syndromes that lead to increased risk of tumors. <i>PTEN</i> restrains tumorigenesis through different mechanisms ranging from phosphatase-dependent and independent activities, subcellular localization and protein interaction, modulating a broad array of cellular functions including growth, proliferation, survival, DNA repair, and cell motility. The main target of <i>PTEN</i> phosphatase activity is one of the most significant cell growth and pro-survival signaling pathway in cancer: PI3K/AKT/mTOR. Several shreds of evidence shed light on the critical role of <i>PTEN</i> in normal and cancer stem cells (CSCs) homeostasis, with its loss fostering the CSC compartment in both solid and hematologic malignancies. CSCs are responsible for tumor propagation, metastatic spread, resistance to therapy, and relapse. Thus, understanding how alterations of <i>PTEN</i> levels affect CSC hallmarks could be crucial for the development of successful therapeutic approaches. Here, we discuss the most significant findings on <i>PTEN</i>-mediated control of CSC state. We aim to unravel the role of <i>PTEN</i> in the regulation of key mechanisms specific for CSCs, such as self-renewal, quiescence/cell cycle, Epithelial-to-Mesenchymal-Transition (EMT), with a particular focus on <i>PTEN</i>-based therapy resistance mechanisms and their exploitation for novel therapeutic approaches in cancer treatment.https://www.mdpi.com/2072-6694/11/8/1076cancer stem cellsPTENtherapy resistancetargeted therapy |
| spellingShingle | Francesca Luongo Francesca Colonna Federica Calapà Sara Vitale Micol E. Fiori Ruggero De Maria PTEN Tumor-Suppressor: The Dam of Stemness in Cancer Cancers cancer stem cells PTEN therapy resistance targeted therapy |
| title | PTEN Tumor-Suppressor: The Dam of Stemness in Cancer |
| title_full | PTEN Tumor-Suppressor: The Dam of Stemness in Cancer |
| title_fullStr | PTEN Tumor-Suppressor: The Dam of Stemness in Cancer |
| title_full_unstemmed | PTEN Tumor-Suppressor: The Dam of Stemness in Cancer |
| title_short | PTEN Tumor-Suppressor: The Dam of Stemness in Cancer |
| title_sort | pten tumor suppressor the dam of stemness in cancer |
| topic | cancer stem cells PTEN therapy resistance targeted therapy |
| url | https://www.mdpi.com/2072-6694/11/8/1076 |
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