Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma

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da Costa, Bruno Cesar ; Dourado, Mauricio Rocha ; de Moraes, Everton Freitas ; Panini, Luana Mari ; Elseragy, Amr ; Teo, Fabio Haach ; Guimaraes, Gustavo Narvaes ; Machado, Renato Assis ; Risteli, Maija ; Gurgel Rocha, Clarissa Araujo ; Ribeiro Paranaiba, Livia Maris ; Gonzalez-Arriagada, Wilfredo Alejandro ; da Silva, Sabrina Daniela ; Carrinho Ayroza Rangel, Ana Lucia ; Marques, Marcelo Rocha ; Salo, Tuula ; Coletta, Ricardo D.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ORAL PATHOLOGY & MEDICINE; v. 52, n. 7, p. 9-pg., 2023-05-29.

Resumo

Background: The expression of heat-shock protein 47 (HSP47) has been linked to collagen synthesis control and implicated in fibrotic disorders, but more recent studies have demonstrated its role in solid tumors. In this study, we explored the prognostic impact of HSP47 in oral squamous cell carcinomas (OSCC) and determined the in vitro effects of its loss-of-function on viability, proliferation, migration, invasion, and resistance to cisplatin of OSCC cells.Methods: The HSP47 expression in tumor samples was assessed by immunohistochemistry in two independent cohorts totaling 339 patients with OSCC, and protein levels were associated with clinicopathological features and survival outcomes. The OSCC cell lines HSC3 and SCC9 were transduced with lentivirus expressing short hairpin RNA to stably silence HSP47 and used in assays to measure cellular viability, proliferation, migration, and invasion.Results: HSP47 was overexpressed in OSCC samples, and its overexpression was significantly and independently associated with poor disease-specific survival and shortened disease-free survival in both OSCC cohorts. The knockdown of HSP47 showed no effects on cell viability or cisplatin sensitivity, but impaired significantly proliferation, migration, and invasion of OSCC cells, with stronger effects on SCC9 cells.Conclusion: Our results show a significant prognostic impact of HSP47 overexpression in OSCC and reveal that HSP47 inhibition impairs the proliferation, migration, and invasion of OSCC cells. HSP47 may represent a potential therapeutic target for OSCC. (AU)

• Processo FAPESP: 21/08943-8 - Impact of the stress-induced phosphoprotein 1 (STIP1) expression in oral squamous cell carcinoma
• Beneficiário: Bruno Cesar da Costa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 22/01123-8 - Impacto da neutralização de SERPINH1 (serpin family H member 1) na resposta das células de carcinoma de células escamosas oral à cisplatina
• Beneficiário: Luana Marí Panini
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 21/13595-9 - Impacto prognóstico da associação do sistema de classificação histopatológica com budding tumoral, proporção tumor-estroma e linfócitos infiltrantes do tumor em pacientes com carcinoma de células escamosas oral em estágio clínico inicial.
• Beneficiário: Gabriela Vivili Domingues Silva
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 22/00994-5 - Análise dos efeitos do Kaempferol na supressão da quimiorresistência induzida pela transição epitélio-mesenquimal em Carcinoma de Células Escamosas Oral
• Beneficiário: Everton Freitas de Morais
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/16077-6 - Análise do Valor Prognóstico e Papel Biológico de Proteínas Superexpressas no Carcinoma de Células Escamosas Oral Identificadas por Meio de Proteômica Baseada em Espectrometria de Massas
• Beneficiário: Ricardo Della Coletta
• Modalidade de apoio: Auxílio à Pesquisa - Regular