Hemoxygenase-1 promotes head and neck cancer cell viability

Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron...

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Detalhes bibliográficos
Autores: Mascaró, Marilina, Alonso, Exequiel Gonzalo, Schweitzer, Karen, Rabassa, Martín Enrique, Carballido, Jessica Andrea, Ibarra, Agustina, Alonso, Eliana Noelia, Bermúdez, Vicente, Fernández Chávez, Lucía, Colo, Georgina Pamela, Ferronato, María Julia, Pichel, Pamela, Recio, Sergio, Clemente, Valentina, Fermento, María Eugenia, Facchinetti, Maria Marta, Curino, Alejandro Carlos
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/202187
Acesso em linha:http://hdl.handle.net/11336/202187
Access Level:Acceso aberto
Palavra-chave:CANCER
HEAD AND NECK
HEMOXYGENASE-1
NUCLEUS
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo:Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron and biliverdin. We have previously reported that HO-1 protein is upregulated in human HNSCC samples and that it is localized in the cytoplasmic and nuclear compartments; additionally, we have demonstrated that HO-1 nuclear localization is associated with malignant progression. In this work, by using pharmacological and genetic experimental approaches, we begin to elucidate the mechanisms through which HO-1 plays a role in HNSCC. We found that high HO-1 mRNA was associated with decreased patient survival in early stages of HNSCC. In vitro experiments have shown that full-length HO-1 localizes in the cytoplasm, and that, depending on its enzymatic activity, it increases cell viability and promotes cell cycle progression. Instead, HO-1 does not alter migration capacity. Furthermore, we show that C-terminal truncated HO-1 localizes into the nucleus, increases cell viability and promotes cell cycle progression. In conclusion, we herein demonstrate that HO-1 displays protumor activities in HNSCC that depend, at least in part, on the nuclear localization of HO-1.

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