CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance
Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in cl...
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MDPI AG
2024-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/3/240 |
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| author | Naji Kharouf Thomas W. Flanagan Abdulhadi A. Alamodi Youssef Al Hmada Sofie-Yasmin Hassan Hosam Shalaby Simeon Santourlidis Sarah-Lilly Hassan Youssef Haikel Mossad Megahed Robert T. Brodell Mohamed Hassan |
| author_facet | Naji Kharouf Thomas W. Flanagan Abdulhadi A. Alamodi Youssef Al Hmada Sofie-Yasmin Hassan Hosam Shalaby Simeon Santourlidis Sarah-Lilly Hassan Youssef Haikel Mossad Megahed Robert T. Brodell Mohamed Hassan |
| author_sort | Naji Kharouf |
| collection | DOAJ |
| description | Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent subpopulations including a small fraction of cancer stem-like cells (CSCs) and non-cancer stem cells (non-CSCs) that make the most of the tumor mass. Like other CSCs, melanoma stem-like cells (MSCs) are characterized by their unique cell surface proteins/stemness markers and aberrant signaling pathways. In addition to its function as a robust marker for stemness properties, CD133 is crucial for the maintenance of stemness properties and drug resistance. Herein, the role of CD133-dependent activation of PI3K/mTOR in the regulation of melanoma progression, drug resistance, and recurrence is reviewed. |
| first_indexed | 2024-03-08T03:59:15Z |
| format | Article |
| id | doaj.art-111dfdca61ce460eaa5ef53f992e1f1f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T03:59:15Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-111dfdca61ce460eaa5ef53f992e1f1f2024-02-09T15:09:41ZengMDPI AGCells2073-44092024-01-0113324010.3390/cells13030240CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug ResistanceNaji Kharouf0Thomas W. Flanagan1Abdulhadi A. Alamodi2Youssef Al Hmada3Sofie-Yasmin Hassan4Hosam Shalaby5Simeon Santourlidis6Sarah-Lilly Hassan7Youssef Haikel8Mossad Megahed9Robert T. Brodell10Mohamed Hassan11Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, FranceDepartment of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, USACollege of Health Sciences, Jackson State University, Jackson, MS 39213, USADepartment of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Pharmacy, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Dusseldorf, GermanyDepartment of Urology, School of Medicine, Tulane University, New Orleans, LA 70112, USAEpigenetics Core Laboratory, Institute of Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Chemistry, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Dusseldorf, GermanyInstitut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, FranceClinic of Dermatology, University Hospital of Aachen, 52074 Aachen, GermanyDepartment of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USAInstitut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, FranceMelanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent subpopulations including a small fraction of cancer stem-like cells (CSCs) and non-cancer stem cells (non-CSCs) that make the most of the tumor mass. Like other CSCs, melanoma stem-like cells (MSCs) are characterized by their unique cell surface proteins/stemness markers and aberrant signaling pathways. In addition to its function as a robust marker for stemness properties, CD133 is crucial for the maintenance of stemness properties and drug resistance. Herein, the role of CD133-dependent activation of PI3K/mTOR in the regulation of melanoma progression, drug resistance, and recurrence is reviewed.https://www.mdpi.com/2073-4409/13/3/240melanomaCSCsCD133PI3KAKTmTOR |
| spellingShingle | Naji Kharouf Thomas W. Flanagan Abdulhadi A. Alamodi Youssef Al Hmada Sofie-Yasmin Hassan Hosam Shalaby Simeon Santourlidis Sarah-Lilly Hassan Youssef Haikel Mossad Megahed Robert T. Brodell Mohamed Hassan CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance Cells melanoma CSCs CD133 PI3K AKT mTOR |
| title | CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance |
| title_full | CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance |
| title_fullStr | CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance |
| title_full_unstemmed | CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance |
| title_short | CD133-Dependent Activation of Phosphoinositide 3-Kinase /AKT/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance |
| title_sort | cd133 dependent activation of phosphoinositide 3 kinase akt mammalian target of rapamycin signaling in melanoma progression and drug resistance |
| topic | melanoma CSCs CD133 PI3K AKT mTOR |
| url | https://www.mdpi.com/2073-4409/13/3/240 |
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