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

Author:

da Costa Bruno Cesar1ORCID,Dourado Mauricio Rocha1ORCID,de Moraes Everton Freitas1ORCID,Panini Luana Marí1,Elseragy Amr2,Téo Fábio Haach1,Guimarães Gustavo Narvaes3ORCID,Machado Renato Assis1ORCID,Risteli Maija2,Gurgel Rocha Clarissa Araujo4ORCID,Paranaíba Lívia Máris Ribeiro5,González‐Arriagada Wilfredo Alejandro6ORCID,da Silva Sabrina Daniela7,Rangel Ana Lucia Carrinho Ayroza8,Marques Marcelo Rocha3,Salo Tuula29,Coletta Ricardo D.1ORCID

Affiliation:

1. Department of Oral Diagnosis and Graduate Program in Oral Biology Piracicaba Dental School, University of Campinas Piracicaba São Paulo Brazil

2. Research Unit of Population Health, University of Oulu, Medical Research Centre and Oulu University Hospital Oulu Finland

3. Department of Biosciences and Graduate Program in Oral Biology Piracicaba Dental School, University of Campinas Piracicaba São Paulo Brazil

4. Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Federal University of Bahia and Dor Institute Salvador Bahia Brazil

5. Department of Pathology and Parasitology Institute of Biomedical Sciences, Federal University of Alfenas Alfenas Minas Gerais Brazil

6. Facultad de Odontología and Centro de Investigación e Innovación Biomédica (CIIB), Universidad de los Andes Santiago Chile

7. Lady Davis Institute for Medical Research and Segal Cancer Center, Jewish General Hospital, and Department of Otolaryngology‐Head and Neck Surgery, McGill University Montreal Quebec Canada

8. Department of Oral Pathology and Oral Medicine Dental School, Western Paraná State University Cascavel Paraná Brazil

9. Department of Oral and Maxillofacial Diseases and Department of Pathology Helsinki University Central Hospital, and Translational Immunology Research Program, University of Helsinki Helsinki Finland

Abstract

AbstractBackgroundThe 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.MethodsThe 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.ResultsHSP47 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.ConclusionOur 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.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação de Amparo à Pesquisa do Estado de Minas Gerais

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Wiley

Subject

Periodontics,Cancer Research,Otorhinolaryngology,Oral Surgery,Pathology and Forensic Medicine

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