Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration

The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a h...

Descripción completa

Detalles Bibliográficos
Autores: Pérez-García, Jessica, Martel Martel, Abel Jesús, García-Vallés, Paula, Corchete, Luis A., García, Juan L., Gestoso-Uzal, Nerea, Vidal-Tocino, Rosario, Blanco, Óscar, Méndez Sánchez, Lucía, Sánchez-Martín, M., Fuentes, Manuel, Herrero, Ana B., Holowatyj, Andreana N., Perea, José, González-Sarmiento, Rogelio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/286313
Acceso en línea:http://hdl.handle.net/10261/286313
Access Level:acceso abierto
Palabra clave:Cell migration
Early-onset colorectal cancer
NOMO1
OMICS
id ES_15ce0dc4e36941468cb9b1d8497b76ca
oai_identifier_str oai:digital.csic.es:10261/286313
network_acronym_str ES
network_name_str España
repository_id_str
spelling Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migrationPérez-García, JessicaMartel Martel, Abel JesúsGarcía-Vallés, PaulaCorchete, Luis A.García, Juan L.Gestoso-Uzal, NereaVidal-Tocino, RosarioBlanco, ÓscarMéndez Sánchez, LucíaSánchez-Martín, M.Fuentes, ManuelHerrero, Ana B.Holowatyj, Andreana N.Perea, JoséGonzález-Sarmiento, RogelioCell migrationEarly-onset colorectal cancerNOMO1OMICSThe incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 (NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1, there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC–IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial–mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.This study was supported by the health research program of the Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness, PI20/01569 and PI20/0974), co-funded by FEDER funds, and Mutua Madrileña Foundation (FMM20/001). A.M.-M was supported by a predoctoral research grant from the Dr. Moraza Fundation (FMoraza18/001). P.G.V and N.G.-U were supported by a predoctoral research grant from the Consejería de Educación—Junta de Castilla y León. A.N.H. was supported by the National Institutes of Health K12 HD043483 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.Multidisciplinary Digital Publishing InstituteInstituto de Salud Carlos IIIEuropean CommissionFundación Mutua MadrileñaJunta de Castilla y LeónNational Institutes of Health (US)Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/286313reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésPérez-García, Jessica; Martel Martel, Abel Jesús; García-Vallés, Paula; Corchete, Luis A.; García, Juan L.; Gestoso-Uzal, Nerea; Vidal-Tocino, Rosario; Blanco, Óscar; Méndez Sánchez, Lucía; Sánchez-Martín, M. ; Fuentes, Manuel; Herrero, Ana B.; Holowatyj, Andreana N.; Perea, José; González-Sarmiento, Rogelio; 2022; Transcriptional profile of NOMO1 knockout cell lines [Dataset]; GEO - Gene Expression Omnibushttp://dx.doi.org/10.3390/cancers14164029Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2863132026-05-22T06:33:51Z
dc.title.none.fl_str_mv Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
title Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
spellingShingle Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
Pérez-García, Jessica
Cell migration
Early-onset colorectal cancer
NOMO1
OMICS
title_short Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
title_full Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
title_fullStr Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
title_full_unstemmed Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
title_sort Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration
dc.creator.none.fl_str_mv Pérez-García, Jessica
Martel Martel, Abel Jesús
García-Vallés, Paula
Corchete, Luis A.
García, Juan L.
Gestoso-Uzal, Nerea
Vidal-Tocino, Rosario
Blanco, Óscar
Méndez Sánchez, Lucía
Sánchez-Martín, M.
Fuentes, Manuel
Herrero, Ana B.
Holowatyj, Andreana N.
Perea, José
González-Sarmiento, Rogelio
author Pérez-García, Jessica
author_facet Pérez-García, Jessica
Martel Martel, Abel Jesús
García-Vallés, Paula
Corchete, Luis A.
García, Juan L.
Gestoso-Uzal, Nerea
Vidal-Tocino, Rosario
Blanco, Óscar
Méndez Sánchez, Lucía
Sánchez-Martín, M.
Fuentes, Manuel
Herrero, Ana B.
Holowatyj, Andreana N.
Perea, José
González-Sarmiento, Rogelio
author_role author
author2 Martel Martel, Abel Jesús
García-Vallés, Paula
Corchete, Luis A.
García, Juan L.
Gestoso-Uzal, Nerea
Vidal-Tocino, Rosario
Blanco, Óscar
Méndez Sánchez, Lucía
Sánchez-Martín, M.
Fuentes, Manuel
Herrero, Ana B.
Holowatyj, Andreana N.
Perea, José
González-Sarmiento, Rogelio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Fundación Mutua Madrileña
Junta de Castilla y León
National Institutes of Health (US)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cell migration
Early-onset colorectal cancer
NOMO1
OMICS
topic Cell migration
Early-onset colorectal cancer
NOMO1
OMICS
description The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 (NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1, there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC–IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial–mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/286313
url http://hdl.handle.net/10261/286313
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Pérez-García, Jessica; Martel Martel, Abel Jesús; García-Vallés, Paula; Corchete, Luis A.; García, Juan L.; Gestoso-Uzal, Nerea; Vidal-Tocino, Rosario; Blanco, Óscar; Méndez Sánchez, Lucía; Sánchez-Martín, M. ; Fuentes, Manuel; Herrero, Ana B.; Holowatyj, Andreana N.; Perea, José; González-Sarmiento, Rogelio; 2022; Transcriptional profile of NOMO1 knockout cell lines [Dataset]; GEO - Gene Expression Omnibus
http://dx.doi.org/10.3390/cancers14164029
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403816554659840
score 15,198674

Similares en LA Referencia