Maria Castejon Grinan

@cabimer.es

Molecular Oncology and Targeted Therapies
Postdoctoral researcher

Maria Castejon Grinan


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https://researchid.co/castejon-grinanm
8

Scopus Publications

146

Scholar Citations

7

Scholar h-index

6

Scholar i10-index

Scopus Publications

  • PICH deficiency limits the progression of MYC-induced B-cell lymphoma
    María Castejón-Griñán, Eliene Albers, Lucía Simón-Carrasco, Paula Aguilera, Mauro Sbroggio, David Pladevall-Morera, Andreas Ingham, Ernest Lim, Alba Guillen-Benitez, Elena Pietrini, Michael Lisby, Ian D. Hickson, Andres J. Lopez-Contreras
    Blood Cancer Journal, 2024
    Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, particularly in lymphomas such as Burkitt lymphoma, which is caused by MYC translocations. To investigate the relevance of PICH in cancer development and progression, we have combined novel PICH-deficient mouse models with the Eμ-Myc transgenic mouse model, which recapitulates B-cell lymphoma development. We have observed that PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females. Moreover, using a Pich conditional knockout mouse model, we have found that Pich deletion in adult mice improves the survival of Eμ-Myc transgenic mice. Notably, we show that Pich deletion in healthy adult mice is well tolerated, supporting PICH as a suitable target for anticancer therapies. Finally, we have corroborated these findings in two human Burkitt lymphoma cell lines and we have found that the death of cancer cells was accompanied by chromosomal instability. Based on these findings, we propose PICH as a potential therapeutic target for Burkitt lymphoma and for other cancers where PICH is overexpressed.
  • Melanoma-associated melanocortin 1 receptor variants confer redox signaling-dependent protection against oxidative DNA damage
    María Castejón-Griñán, Sonia Cerdido, José Sánchez-Beltrán, Ana Lambertos, Marta Abrisqueta, Cecilia Herraiz, Celia Jiménez-Cervantes, José Carlos García-Borrón
    Redox Biology, 2024
    Cutaneous melanoma, a lethal skin cancer, arises from malignant transformation of melanocytes. Solar ultraviolet radiation (UVR) is a major environmental risk factor for melanoma since its interaction with the skin generates DNA damage, either directly or indirectly via oxidative stress. Pheomelanin pigments exacerbate oxidative stress in melanocytes by UVR-dependent and independent mechanisms. Thus, oxidative stress is considered to contribute to melanomagenesis, particularly in people with pheomelanic pigmentation. The melanocortin 1 receptor gene (MC1R) is a major melanoma susceptibility gene. Frequent MC1R variants (varMC1R) associated with fair skin and red or yellow hair color display hypomorphic signaling to the cAMP pathway and are associated with higher melanoma risk. This association is thought to be due to production of photosensitizing pheomelanins as well as deficient induction of DNA damage repair downstream of varMC1R. However, the data on modulation of oxidative DNA damage repair by MC1R remain scarce. We recently demonstrated that varMC1R accelerates clearance of reactive oxygen species (ROS)-induced DNA strand breaks in an AKT-dependent manner. Here we show that varMC1R also protects against ROS-dependent formation of 8-oxodG, the most frequent oxidative DNA lesion. Since the base excision repair (BER) pathway mediates clearance of these DNA lesions, we analyzed induction of BER enzymes in human melanoma cells of varMC1R genotype. Agonist-mediated activation of both wildtype (wtMC1R) and varMC1R significantly induced OGG and APE-1/Ref1, the rate-limiting BER enzymes responsible for repair of 8-oxodG. Moreover, we found that NADPH oxidase (NOX)-dependent generation of ROS was responsible for AKT activation and oxidative DNA damage repair downstream of varMC1R. These observations provide a better understanding of the functional properties of melanoma-associated MC1R alleles and may be useful for the rational development of strategies to correct defective varMC1R responses for efficient photoprotection and melanoma prevention in fair-skinned individuals.
  • MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42
    S. Cerdido, M. Abrisqueta, J. Sánchez-Beltrán, A. Lambertos, M. Castejón-Griñán, C. Muñoz, C. Olivares, J.C. García-Borrón, C. Jiménez-Cervantes, C. Herraiz
    Cancer Letters, 2024
  • ATRX-Deficient High-Grade Glioma Cells Exhibit Increased Sensitivity to RTK and PDGFR Inhibitors
    David Pladevall-Morera, María Castejón-Griñán, Paula Aguilera, Karina Gaardahl, Andreas Ingham, Jacqueline A. Brosnan-Cashman, Alan K. Meeker, Andres J. Lopez-Contreras
    Cancers, 2022
    High-grade glioma, including anaplastic astrocytoma and glioblastoma (GBM) patients, have a poor prognosis due to the lack of effective treatments. Therefore, the development of new therapeutic strategies to treat these gliomas is urgently required. Given that high-grade gliomas frequently harbor mutations in the SNF2 family chromatin remodeler ATRX, we performed a screen to identify FDA-approved drugs that are toxic to ATRX-deficient cells. Our findings reveal that multi-targeted receptor tyrosine kinase (RTK) and platelet-derived growth factor receptor (PDGFR) inhibitors cause higher cellular toxicity in high-grade glioma ATRX-deficient cells. Furthermore, we demonstrate that a combinatorial treatment of RTKi with temozolomide (TMZ)–the current standard of care treatment for GBM patients–causes pronounced toxicity in ATRX-deficient high-grade glioma cells. Our findings suggest that combinatorial treatments with TMZ and RTKi may increase the therapeutic window of opportunity in patients who suffer high-grade gliomas with ATRX mutations. Thus, we recommend incorporating the ATRX status into the analyses of clinical trials with RTKi and PDGFRi.
  • Mahogunin ring finger 1 is required for genomic stability and modulates the malignant phenotype of melanoma cells
    Idoya Martínez-Vicente, Marta Abrisqueta, Cecilia Herraiz, Julia Sirés-Campos, María Castejón-Griñán, Dorothy C. Bennett, Conchi Olivares, Jose Carlos García-Borrón, Celia Jiménez-Cervantes
    Cancers, 2020
    The mouse mahoganoid mutation abrogating Mahogunin Ring Finger-1 (MGRN1) E3 ubiquitin ligase expression causes hyperpigmentation, congenital heart defects and neurodegeneration. To study the pathophysiology of MGRN1 loss, we compared Mgrn1-knockout melanocytes with genetically matched controls and melan-md1 (mahoganoid) melanocytes. MGRN1 knockout induced a more differentiated and adherent phenotype, decreased motility, increased the percentage of cells in the S phase of the cell cycle and promoted genomic instability, as shown by stronger γH2AX labelling, increased burden of DNA breaks and higher abundance of aneuploid cells. Lack of MGRN1 expression decreased the ability of melanocytes to cope with DNA breaks generated by oxidizing agents or hydroxyurea-induced replicative stress, suggesting a contribution of genomic instability to the mahoganoid phenotype. MGRN1 knockout in B16-F10 melanoma cells also augmented pigmentation, increased cell adhesion to collagen, impaired 2D and 3D motility and caused genomic instability. Tumors formed by Mgrn1-KO B16-F10 cells had lower mitotic indices, fewer Ki67-positive cells and showed a trend towards smaller size. In short-term lung colonization assays Mgrn1-KO cells showed impaired colonization potential. Moreover, lower expression of MGRN1 is significantly associated with better survival of human melanoma patients. Therefore, MGRN1 might be an important phenotypic determinant of melanoma cells.
  • CAMP-independent non-pigmentary actions of variant melanocortin 1 receptor: AKT-mediated activation of protective responses to oxidative DNA damage
    María Castejón-Griñán, Cecilia Herraiz, Conchi Olivares, Celia Jiménez-Cervantes, Jose Carlos García-Borrón
    Oncogene, 2018
  • Human melanocortin 1 receptor-mediated ubiquitination of nonvisual arrestins. Role of Mahogunin Ring Finger 1 E3 ligase
    Marta Abrisqueta, Concepción Olivares, Cecilia Herraiz, María Castejón-Griñán, Julia Sirés-Campos, José C. García-Borrón, Celia Jiménez-Cervantes
    Biochimica Et Biophysica Acta Molecular Cell Research, 2018
  • Functional characterization of MC1R-TUBB3 intergenic splice variants of the human melanocortin 1 receptor
    Cecilia Herraiz, Conchi Olivares, Maria Castejón-Griñán, Marta Abrisqueta, Celia Jiménez-Cervantes, José Carlos García-Borrón
    Plos One, 2015
    The melanocortin 1 receptor gene (MC1R) expressed in melanocytes is a major determinant of skin pigmentation. It encodes a Gs protein-coupled receptor activated by α-melanocyte stimulating hormone (αMSH). Human MC1R has an inefficient poly(A) site allowing intergenic splicing with its downstream neighbour Tubulin-β-III (TUBB3). Intergenic splicing produces two MC1R isoforms, designated Iso1 and Iso2, bearing the complete seven transmembrane helices from MC1R fused to TUBB3-derived C-terminal extensions, in-frame for Iso1 and out-of-frame for Iso2. It has been reported that exposure to ultraviolet radiation (UVR) might promote an isoform switch from canonical MC1R (MC1R-001) to the MC1R-TUBB3 chimeras, which might lead to novel phenotypes required for tanning. We expressed the Flag epitope-tagged intergenic isoforms in heterologous HEK293T cells and human melanoma cells, for functional characterization. Iso1 was expressed with the expected size. Iso2 yielded a doublet of Mr significantly lower than predicted, and impaired intracellular stability. Although Iso1- and Iso2 bound radiolabelled agonist with the same affinity as MC1R-001, their plasma membrane expression was strongly reduced. Decreased surface expression mostly resulted from aberrant forward trafficking, rather than high rates of endocytosis. Functional coupling of both isoforms to cAMP was lower than wild-type, but ERK activation upon binding of αMSH was unimpaired, suggesting imbalanced signaling from the splice variants. Heterodimerization of differentially labelled MC1R-001 with the splicing isoforms analyzed by co-immunoprecipitation was efficient and caused decreased surface expression of binding sites. Thus, UVR-induced MC1R isoforms might contribute to fine-tune the tanning response by modulating MC1R-001 availability and functional parameters.

RECENT SCHOLAR PUBLICATIONS

  • Mahogunin Ring Finger 1, a possible melanoma biomarker, is required for normal cell cycle progression and genomic stability
    J Sanchez-Beltran, I Martinez-Vicente, M Castejon-Grinan, ...
    FEBS OPEN BIO 14, 308-309 , 2024
    2024
  • Melanoma-associated melanocortin 1 receptor variants confer redox signaling-dependent protection against oxidative DNA damage
    M Castejón-Griñán, S Cerdido, J Sánchez-Beltrán, A Lambertos, ...
    Redox Biology 72, 103135 , 2024
    2024
    Citations: 19
  • MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42
    S Cerdido, M Abrisqueta, J Sánchez-Beltrán, A Lambertos, ...
    Cancer Letters 581, 216484 , 2024
    2024
    Citations: 13
  • PICH deficiency limits the progression of MYC-induced B-cell lymphoma
    M Castejón-Griñán, E Albers, L Simón-Carrasco, P Aguilera, M Sbroggio, ...
    Blood Cancer Journal 14 (1), 16 , 2024
    2024
    Citations: 4
  • PICH is a potential therapeutic target for Burkitt Lymphoma
    M Castejón-Griñán, E Albers, D Pladevall-Morera, AJ López-Contreras
    2022
  • ATRX-deficient high-grade glioma cells exhibit increased sensitivity to RTK and PDGFR inhibitors
    D Pladevall-Morera, M Castejón-Griñán, P Aguilera, K Gaardahl, ...
    Cancers 14 (7), 1790 , 2022
    2022
    Citations: 15
  • Mahogunin ring finger 1 is required for genomic stability and modulates the malignant phenotype of melanoma cells
    I Martínez-Vicente, M Abrisqueta, C Herraiz, J Sirés-Campos, ...
    Cancers 12 (10), 2840 , 2020
    2020
    Citations: 7
  • Melanocortin 1 Receptor as regulator of protective responses against oxidative stress and UVR-induced DNA damage
    M Castejón Griñán
    Melanocortin 1 Receptor as regulator of protective responses against … , 2019
    2019
  • Inestabilidad genómica y progresión aberrante del ciclo celular en melanocitos Mgrn1-Ko
    IM Vicente, MA González, M Castejón, JS Campos, MCO Sánchez, ...
    IV Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2019
    2019
  • Actions of variant melanocortin 1 receptor: akt-mediated activation of protective responses to oxidative DNA damage
    M Castejón, CMH Serrano, JS Campos, MA González, IM Vicente, ...
    IV Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2019
    2019
  • El receptor de melanocortinas 1 (MC1R) como regulador de respuestas de defensa frente al estrés oxidativo, daño inducido por la radiación ultravioleta
    M Castejón Griñán
    2019
  • cAMP-independent non-pigmentary actions of variant melanocortin 1 receptor: AKT-mediated activation of protective responses to oxidative DNA damage
    M Castejon-Grinan, C Herraiz, C Olivares, C Jimenez-Cervantes, ...
    Oncogene 37 (27), 3631-3646 , 2018
    2018
    Citations: 52
  • Human melanocortin 1 receptor-mediated ubiquitination of nonvisual arrestins. Role of Mahogunin Ring Finger 1 E3 ligase
    M Abrisqueta, C Olivares, C Herraiz, M Castejón-Griñán, J Sirés-Campos, ...
    Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1865 (1), 76-94 , 2018
    2018
    Citations: 13
  • BLOG COMO RECURSO DIDÁCTICO PARA LA ENSEÑANZA DEL CONTENIDO NUTRICIÓN INDISPENSABLE PARA LA SALUD INTEGRAL ADAPTADO AL 1ER AÑO DE EDUCACION MEDIA DEL CB “DOMINGO HURTADO …
    M Castejón
    TRABAJO DE GRADO DE MAESTRÍA , 2017
    2017
  • Mgrn1: proteína reguladora de la proliferación y diferenciación de los melanocitos
    IM Vicente, MA González, M Castejón, JS Campos, MCO Sánchez, ...
    III Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2017
    2017
  • Mahogunin RING Finger 1 regulates pigmentation by modulation of the melanosomal pH J
    JS Campos, M Castejón, IM Vicente, MA González, C Herraiz, ...
    III Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2017
    2017
  • Functional characterization of MC1R-TUBB3 intergenic splice variants of the human melanocortin 1 receptor
    C Herraiz, C Olivares, M Castejón-Griñán, M Abrisqueta, ...
    PloS one 10 (12), e0144757 , 2015
    2015
    Citations: 23

MOST CITED SCHOLAR PUBLICATIONS

  • cAMP-independent non-pigmentary actions of variant melanocortin 1 receptor: AKT-mediated activation of protective responses to oxidative DNA damage
    M Castejon-Grinan, C Herraiz, C Olivares, C Jimenez-Cervantes, ...
    Oncogene 37 (27), 3631-3646 , 2018
    2018
    Citations: 52
  • Functional characterization of MC1R-TUBB3 intergenic splice variants of the human melanocortin 1 receptor
    C Herraiz, C Olivares, M Castejón-Griñán, M Abrisqueta, ...
    PloS one 10 (12), e0144757 , 2015
    2015
    Citations: 23
  • Melanoma-associated melanocortin 1 receptor variants confer redox signaling-dependent protection against oxidative DNA damage
    M Castejón-Griñán, S Cerdido, J Sánchez-Beltrán, A Lambertos, ...
    Redox Biology 72, 103135 , 2024
    2024
    Citations: 19
  • ATRX-deficient high-grade glioma cells exhibit increased sensitivity to RTK and PDGFR inhibitors
    D Pladevall-Morera, M Castejón-Griñán, P Aguilera, K Gaardahl, ...
    Cancers 14 (7), 1790 , 2022
    2022
    Citations: 15
  • MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42
    S Cerdido, M Abrisqueta, J Sánchez-Beltrán, A Lambertos, ...
    Cancer Letters 581, 216484 , 2024
    2024
    Citations: 13
  • Human melanocortin 1 receptor-mediated ubiquitination of nonvisual arrestins. Role of Mahogunin Ring Finger 1 E3 ligase
    M Abrisqueta, C Olivares, C Herraiz, M Castejón-Griñán, J Sirés-Campos, ...
    Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1865 (1), 76-94 , 2018
    2018
    Citations: 13
  • Mahogunin ring finger 1 is required for genomic stability and modulates the malignant phenotype of melanoma cells
    I Martínez-Vicente, M Abrisqueta, C Herraiz, J Sirés-Campos, ...
    Cancers 12 (10), 2840 , 2020
    2020
    Citations: 7
  • PICH deficiency limits the progression of MYC-induced B-cell lymphoma
    M Castejón-Griñán, E Albers, L Simón-Carrasco, P Aguilera, M Sbroggio, ...
    Blood Cancer Journal 14 (1), 16 , 2024
    2024
    Citations: 4
  • Mahogunin Ring Finger 1, a possible melanoma biomarker, is required for normal cell cycle progression and genomic stability
    J Sanchez-Beltran, I Martinez-Vicente, M Castejon-Grinan, ...
    FEBS OPEN BIO 14, 308-309 , 2024
    2024
  • PICH is a potential therapeutic target for Burkitt Lymphoma
    M Castejón-Griñán, E Albers, D Pladevall-Morera, AJ López-Contreras
    2022
  • Melanocortin 1 Receptor as regulator of protective responses against oxidative stress and UVR-induced DNA damage
    M Castejón Griñán
    Melanocortin 1 Receptor as regulator of protective responses against … , 2019
    2019
  • Inestabilidad genómica y progresión aberrante del ciclo celular en melanocitos Mgrn1-Ko
    IM Vicente, MA González, M Castejón, JS Campos, MCO Sánchez, ...
    IV Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2019
    2019
  • Actions of variant melanocortin 1 receptor: akt-mediated activation of protective responses to oxidative DNA damage
    M Castejón, CMH Serrano, JS Campos, MA González, IM Vicente, ...
    IV Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2019
    2019
  • El receptor de melanocortinas 1 (MC1R) como regulador de respuestas de defensa frente al estrés oxidativo, daño inducido por la radiación ultravioleta
    M Castejón Griñán
    2019
  • BLOG COMO RECURSO DIDÁCTICO PARA LA ENSEÑANZA DEL CONTENIDO NUTRICIÓN INDISPENSABLE PARA LA SALUD INTEGRAL ADAPTADO AL 1ER AÑO DE EDUCACION MEDIA DEL CB “DOMINGO HURTADO …
    M Castejón
    TRABAJO DE GRADO DE MAESTRÍA , 2017
    2017
  • Mgrn1: proteína reguladora de la proliferación y diferenciación de los melanocitos
    IM Vicente, MA González, M Castejón, JS Campos, MCO Sánchez, ...
    III Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2017
    2017
  • Mahogunin RING Finger 1 regulates pigmentation by modulation of the melanosomal pH J
    JS Campos, M Castejón, IM Vicente, MA González, C Herraiz, ...
    III Jornadas Doctorales Escuela Internacional de Doctorado de la Universidad … , 2017
    2017