LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer

Autores
Lindquist, David; Alsina, Fernando Cruz; Herdenberg, Carl; Larsson, Catharina; Höppener, Jo; Wang, Na; Paratcha, Gustavo; Tarján, Miklós; Tot, Tibor; Henriksson, Roger; Hedman, Håkan
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-Type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.
Fil: Lindquist, David. Universidad de Umea; Suecia
Fil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Herdenberg, Carl. Universidad de Umea; Suecia
Fil: Larsson, Catharina. Karolinska University Hospital;
Fil: Höppener, Jo. University Medical Center Utrecht;
Fil: Wang, Na. Karolinska University Hospital;
Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Tarján, Miklós. Falu Lasarett; Suecia
Fil: Tot, Tibor. Falu Lasarett; Suecia
Fil: Henriksson, Roger. Universidad de Umea; Suecia
Fil: Hedman, Håkan. Universidad de Umea; Suecia
Materia
C634R
LRIG1
M918T
MEN2A
MEN2B
RET
THYROID CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/88093
Acceder
id CONICETDig_99a301d69b991823bf95f83e1df48ecb
oai_identifier_str oai:ri.conicet.gov.ar:11336/88093
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancerLindquist, DavidAlsina, Fernando CruzHerdenberg, CarlLarsson, CatharinaHöppener, JoWang, NaParatcha, GustavoTarján, MiklósTot, TiborHenriksson, RogerHedman, HåkanC634RLRIG1M918TMEN2AMEN2BRETTHYROID CANCERhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-Type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.Fil: Lindquist, David. Universidad de Umea; SueciaFil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Herdenberg, Carl. Universidad de Umea; SueciaFil: Larsson, Catharina. Karolinska University Hospital;Fil: Höppener, Jo. University Medical Center Utrecht;Fil: Wang, Na. Karolinska University Hospital;Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tarján, Miklós. Falu Lasarett; SueciaFil: Tot, Tibor. Falu Lasarett; SueciaFil: Henriksson, Roger. Universidad de Umea; SueciaFil: Hedman, Håkan. Universidad de Umea; SueciaSpandidos Publications2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88093Lindquist, David; Alsina, Fernando Cruz; Herdenberg, Carl; Larsson, Catharina; Höppener, Jo; et al.; LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer; Spandidos Publications; International Journal of Oncology; 52; 4; 4-2018; 1189-11971019-6439CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.spandidos-publications.com/10.3892/ijo.2018.4273info:eu-repo/semantics/altIdentifier/doi/10.3892/ijo.2018.4273info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:01:32Zoai:ri.conicet.gov.ar:11336/88093instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:01:32.601CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
title LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
spellingShingle LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
Lindquist, David
C634R
LRIG1
M918T
MEN2A
MEN2B
RET
THYROID CANCER
title_short LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
title_full LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
title_fullStr LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
title_full_unstemmed LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
title_sort LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
dc.creator.none.fl_str_mv Lindquist, David
Alsina, Fernando Cruz
Herdenberg, Carl
Larsson, Catharina
Höppener, Jo
Wang, Na
Paratcha, Gustavo
Tarján, Miklós
Tot, Tibor
Henriksson, Roger
Hedman, Håkan
author Lindquist, David
author_facet Lindquist, David
Alsina, Fernando Cruz
Herdenberg, Carl
Larsson, Catharina
Höppener, Jo
Wang, Na
Paratcha, Gustavo
Tarján, Miklós
Tot, Tibor
Henriksson, Roger
Hedman, Håkan
author_role author
author2 Alsina, Fernando Cruz
Herdenberg, Carl
Larsson, Catharina
Höppener, Jo
Wang, Na
Paratcha, Gustavo
Tarján, Miklós
Tot, Tibor
Henriksson, Roger
Hedman, Håkan
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv C634R
LRIG1
M918T
MEN2A
MEN2B
RET
THYROID CANCER
topic C634R
LRIG1
M918T
MEN2A
MEN2B
RET
THYROID CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-Type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.
Fil: Lindquist, David. Universidad de Umea; Suecia
Fil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Herdenberg, Carl. Universidad de Umea; Suecia
Fil: Larsson, Catharina. Karolinska University Hospital;
Fil: Höppener, Jo. University Medical Center Utrecht;
Fil: Wang, Na. Karolinska University Hospital;
Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Tarján, Miklós. Falu Lasarett; Suecia
Fil: Tot, Tibor. Falu Lasarett; Suecia
Fil: Henriksson, Roger. Universidad de Umea; Suecia
Fil: Hedman, Håkan. Universidad de Umea; Suecia
description Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-Type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.
publishDate 2018
dc.date.none.fl_str_mv 2018-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/88093
Lindquist, David; Alsina, Fernando Cruz; Herdenberg, Carl; Larsson, Catharina; Höppener, Jo; et al.; LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer; Spandidos Publications; International Journal of Oncology; 52; 4; 4-2018; 1189-1197
1019-6439
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88093
identifier_str_mv Lindquist, David; Alsina, Fernando Cruz; Herdenberg, Carl; Larsson, Catharina; Höppener, Jo; et al.; LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer; Spandidos Publications; International Journal of Oncology; 52; 4; 4-2018; 1189-1197
1019-6439
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.spandidos-publications.com/10.3892/ijo.2018.4273
info:eu-repo/semantics/altIdentifier/doi/10.3892/ijo.2018.4273
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Spandidos Publications
publisher.none.fl_str_mv Spandidos Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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