TY - JOUR
T1 - Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma
AU - da Costa, Bruno Cesar
AU - Dourado, Mauricio Rocha
AU - de Moraes, Everton Freitas
AU - Panini, Luana Marí
AU - Elseragy, Amr
AU - Téo, Fábio Haach
AU - Guimarães, Gustavo Narvaes
AU - Machado, Renato Assis
AU - Risteli, Maija
AU - Gurgel Rocha, Clarissa Araujo
AU - Paranaíba, Lívia Máris Ribeiro
AU - González-Arriagada, Wilfredo Alejandro
AU - da Silva, Sabrina Daniela
AU - Rangel, Ana Lucia Carrinho Ayroza
AU - Marques, Marcelo Rocha
AU - Salo, Tuula
AU - Coletta, Ricardo D.
N1 - Publisher Copyright:
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
KW - SERPINH1
KW - invasion
KW - oral cancer
KW - prognosis
KW - proliferation
UR - http://www.scopus.com/inward/record.url?scp=85161033862&partnerID=8YFLogxK
U2 - 10.1111/jop.13455
DO - 10.1111/jop.13455
M3 - Article
C2 - 37247331
SN - 0904-2512
VL - 52
SP - 601
EP - 609
JO - Journal of Oral Pathology and Medicine
JF - Journal of Oral Pathology and Medicine
IS - 7
ER -