Hippo Pathway in Regulating Drug Resistance of Glioblastoma
Glioblastoma (GBM) represents the most common and malignant tumor of the Central Nervous System (CNS), affecting both children and adults. GBM is one of the deadliest tumor types and it shows a strong multidrug resistance (MDR) and an immunosuppressive microenvironment which remain a great challenge...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13431 |
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| author | Giacomo Casati Laura Giunti Anna Lisa Iorio Arianna Marturano Luisa Galli Iacopo Sardi |
| author_facet | Giacomo Casati Laura Giunti Anna Lisa Iorio Arianna Marturano Luisa Galli Iacopo Sardi |
| author_sort | Giacomo Casati |
| collection | DOAJ |
| description | Glioblastoma (GBM) represents the most common and malignant tumor of the Central Nervous System (CNS), affecting both children and adults. GBM is one of the deadliest tumor types and it shows a strong multidrug resistance (MDR) and an immunosuppressive microenvironment which remain a great challenge to therapy. Due to the high recurrence of GBM after treatment, the understanding of the chemoresistance phenomenon and how to stimulate the antitumor immune response in this pathology is crucial. The deregulation of the Hippo pathway is involved in tumor genesis, chemoresistance and immunosuppressive nature of GBM. This pathway is an evolutionarily conserved signaling pathway with a kinase cascade core, which controls the translocation of YAP (Yes-Associated Protein)/TAZ (Transcriptional Co-activator with PDZ-binding Motif) into the nucleus, leading to regulation of organ size and growth. With this review, we want to highlight how chemoresistance and tumor immunosuppression work in GBM and how the Hippo pathway has a key role in them. We linger on the role of the Hippo pathway evaluating the effect of its de-regulation among different human cancers. Moreover, we consider how different pathways are cross-linked with the Hippo signaling in GBM genesis and the hypothetical mechanisms responsible for the Hippo pathway activation in GBM. Furthermore, we describe various drugs targeting the Hippo pathway. In conclusion, all the evidence described largely support a strong involvement of the Hippo pathway in gliomas progression, in the activation of chemoresistance mechanisms and in the development of an immunosuppressive microenvironment. Therefore, this pathway is a promising target for the treatment of high grade gliomas and in particular of GBM. |
| first_indexed | 2024-03-10T03:55:36Z |
| format | Article |
| id | doaj.art-66da0088914f48de939ae39a62dada85 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:55:36Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-66da0088914f48de939ae39a62dada852023-11-23T08:46:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241343110.3390/ijms222413431Hippo Pathway in Regulating Drug Resistance of GlioblastomaGiacomo Casati0Laura Giunti1Anna Lisa Iorio2Arianna Marturano3Luisa Galli4Iacopo Sardi5Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, 50139 Florence, ItalyNeuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, 50139 Florence, ItalyNeuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, 50139 Florence, ItalyNeuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, 50139 Florence, ItalyInfectious Disease Unit, Department of Health Sciences, University of Florence, 50139 Florence, ItalyNeuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, 50139 Florence, ItalyGlioblastoma (GBM) represents the most common and malignant tumor of the Central Nervous System (CNS), affecting both children and adults. GBM is one of the deadliest tumor types and it shows a strong multidrug resistance (MDR) and an immunosuppressive microenvironment which remain a great challenge to therapy. Due to the high recurrence of GBM after treatment, the understanding of the chemoresistance phenomenon and how to stimulate the antitumor immune response in this pathology is crucial. The deregulation of the Hippo pathway is involved in tumor genesis, chemoresistance and immunosuppressive nature of GBM. This pathway is an evolutionarily conserved signaling pathway with a kinase cascade core, which controls the translocation of YAP (Yes-Associated Protein)/TAZ (Transcriptional Co-activator with PDZ-binding Motif) into the nucleus, leading to regulation of organ size and growth. With this review, we want to highlight how chemoresistance and tumor immunosuppression work in GBM and how the Hippo pathway has a key role in them. We linger on the role of the Hippo pathway evaluating the effect of its de-regulation among different human cancers. Moreover, we consider how different pathways are cross-linked with the Hippo signaling in GBM genesis and the hypothetical mechanisms responsible for the Hippo pathway activation in GBM. Furthermore, we describe various drugs targeting the Hippo pathway. In conclusion, all the evidence described largely support a strong involvement of the Hippo pathway in gliomas progression, in the activation of chemoresistance mechanisms and in the development of an immunosuppressive microenvironment. Therefore, this pathway is a promising target for the treatment of high grade gliomas and in particular of GBM.https://www.mdpi.com/1422-0067/22/24/13431glioblastoma (GBM)signaling pathwaystumor heterogeneitytumor microenvironment (TME)Hippo pathwaychemoresistance |
| spellingShingle | Giacomo Casati Laura Giunti Anna Lisa Iorio Arianna Marturano Luisa Galli Iacopo Sardi Hippo Pathway in Regulating Drug Resistance of Glioblastoma International Journal of Molecular Sciences glioblastoma (GBM) signaling pathways tumor heterogeneity tumor microenvironment (TME) Hippo pathway chemoresistance |
| title | Hippo Pathway in Regulating Drug Resistance of Glioblastoma |
| title_full | Hippo Pathway in Regulating Drug Resistance of Glioblastoma |
| title_fullStr | Hippo Pathway in Regulating Drug Resistance of Glioblastoma |
| title_full_unstemmed | Hippo Pathway in Regulating Drug Resistance of Glioblastoma |
| title_short | Hippo Pathway in Regulating Drug Resistance of Glioblastoma |
| title_sort | hippo pathway in regulating drug resistance of glioblastoma |
| topic | glioblastoma (GBM) signaling pathways tumor heterogeneity tumor microenvironment (TME) Hippo pathway chemoresistance |
| url | https://www.mdpi.com/1422-0067/22/24/13431 |
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