2026-06-14T10:38:28Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/97282025-05-08T10:46:01Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16969col_20.500.12105_16974col_20.500.12105_16977col_20.500.12105_19617
Repisalud
author
López-Valero, Israel
author
Dávila, David
author
González-Martínez, José
author
Salvador-Tormo, Nélida
author
Lorente, Mar
author
Saiz-Ladera, Cristina
author
Torres, Sofía
author
Gabicagogeascoa, Estibaliz
author
Hernández-Tiedra, Sonia
author
García-Taboada, Elena
author
Mendiburu-Eliçabe, Marina
author
Rodríguez-Fornés, Fátima
author
Sánchez-Domínguez, Rebeca
author
Segovia, Jose Carlos
author
Sánchez-Gómez, Pilar
author
Matheu, Ander
author
Sepúlveda, Juan M
author
Velasco, Guillermo
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación Mutua Madrileña
funder
Fundación La Marató TV3
funder
Asociación Española Contra el Cáncer
funder
Pfizer
2020-04-23T17:14:45Z
2020-04-23T17:14:45Z
2020
Theranostics. 2020 Apr 6;10(11):5120-5136.
10.7150/thno.41450
1838-7640
1838-7640
Theranostics
32308772
http://hdl.handle.net/20.500.12105/9728
Glioblastoma (GBM) is one of the most aggressive forms of cancer. It has been proposed that the presence within these tumors of a population of cells with stem-like features termed Glioma Initiating Cells (GICs) is responsible for the relapses that take place in the patients with this disease. Targeting this cell population is therefore an issue of great therapeutic interest in neuro-oncology. We had previously found that the neurotrophic factor MIDKINE (MDK) promotes resistance to glioma cell death. The main objective of this work is therefore investigating the role of MDK in the regulation of GICs. Methods: Assays of gene and protein expression, self-renewal capacity, autophagy and apoptosis in cultures of GICs derived from GBM samples subjected to different treatments. Analysis of the growth of GICs-derived xenografts generated in mice upon blockade of the MDK and its receptor the ALK receptor tyrosine kinase (ALK) upon exposure to different treatments. Results: Genetic or pharmacological inhibition of MDK or ALK decreases the self-renewal and tumorigenic capacity of GICs via the autophagic degradation of the transcription factor SOX9. Blockade of the MDK/ALK axis in combination with temozolomide depletes the population of GICs in vitro and has a potent anticancer activity in xenografts derived from GICs. Conclusions: The MDK/ALK axis regulates the self-renewal capacity of GICs by controlling the autophagic degradation of the transcription factor SOX9. Inhibition of the MDK/ALK axis may be a therapeutic strategy to target GICs in GBM patients.
eng
ALK receptor tyrosine kinase
Midkine
SOX
Autophagy
Combinational therapies
Glioblastoma
Midkine signaling maintains the self-renewal and tumorigenic capacity of glioma initiating cells
research article
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URL
https://repisalud.isciii.es/bitstreams/836a7bec-6cd2-4990-8232-2aa7578ea3d9/download
File
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application/pdf
MidkineSignalingMaintainsThe_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/585ead79-19f1-4ae6-b9b1-2e013e2fcf53/download
File
MD5
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text/plain
MidkineSignalingMaintainsThe_2020.pdf.txt