| Texto completo | |
| Autor(es): Mostrar menos - |
Alves, Marcia Gaiao
[1]
;
Kodama, Marcio Hideki
[1]
;
Marcelino da Silva, Elaine Zayas
[1, 2]
;
Martinelli Gomes, Bruno Belmonte
[1]
;
Alves da Silva, Rodrigo Alberto
[1]
;
Vieira, Gabriel Viliod
[1]
;
Alves, Vani Maria
[1]
;
da Fonseca, Carol Kobori
[1]
;
Santana, Ana Carolina
[1]
;
Cecilio, Nerry Tatiana
[3]
;
Alexandre Costa, Mara Silvia
[1]
;
Jamur, Maria Celia
[1]
;
Oliver, Constance
[1]
;
Cunha, Thiago Mattar
[3]
;
Bugge, Thomas H.
[2]
;
Braz-Silva, Paulo Henrique
[4, 5]
;
Colli, Leandro M.
[6]
;
Sales, Katiuchia Uzzun
[1]
Número total de Autores: 18
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol & Pathogen Bioagents, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, NIH, Bethesda, MD - USA
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Sch Dent, Dept Stomatol, Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Sch Med, Inst Trop Med Sao Paulo, Virol Lab, Sao Paulo, SP - Brazil
[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Image Sci Hematol & Med Oncol, Sao Paulo, SP - Brazil
Número total de Afiliações: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | TRANSLATIONAL ONCOLOGY; v. 14, n. 1 JAN 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
Background: Oral squamous cell carcinoma (OSCC) remains a challenging cancer to treat despite all the advances of the last 50 years. Kallikrein 5 (KLK5) is among the serine proteases implicated in OSCC development. However, whether the activity of KLK5 promotes carcinogenesis is still controversial. Moreover, knowledge regarding the role of the KLK5 cognate inhibitor, Lympho-Epithelial Kazal-Type related Inhibitor (LEKTI), in OSCC is scarce. We have, thus, sought to investigate the importance of KLK5 and LEKTI expression in premalignant and malignant lesions of the oral cavity. Methods: KLK5 and LEKTI protein expression was evaluated in 301 human samples, which were comprised of nonmalignant and malignant lesions of the oral cavity. Moreover, a bioinformatic analysis of the overall survival rate from 517 head and neck squamous cell carcinoma (HNSCC) samples was performed. Additionally, to mimic the uncovered KLK5 to serine peptidase inhibitor (SPINK5) imbalance, the KLK5 gene was abrogated in an OSCC cell line using CRISPR-Cas9 technology. The generated cell line was then used for in vivo and in vitro carcinogenesis related experiments. Results: LEKTI was found to be statistically downregulated in OSCCs, with increased KLK5/SPINK5 mRNA ratio being associated with a shorter overall survival (p = 0.091). Indeed, disruption of KLK5 to SPINK5 balance through the generation of KLK5 null OSCC cells led to smaller xenografted tumors and statistically decreased proliferation rates following multiple time points of BrdU treatment in vitro. Conclusion: The association of increased enzyme/inhibitor ratio with poor prognosis indicates KLK5 to SPINK5 relative expression as an important prognostic marker in OSCC. (AU) | |
| Processo FAPESP: | 14/06316-2 - Estudo genético da via proteolítica da matriptase em câncer de cabeça e pescoço |
| Beneficiário: | Katiuchia Uzzun Sales |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 16/13228-8 - Estudo genético da superexpressão de LEKTI em modelo experimental de câncer de cabeça e pescoço |
| Beneficiário: | Elaine Zayas Marcelino da Silva |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 16/16715-7 - Regulação da atividade do inibidor do ativador do fator de crescimento de hepatócitos (Hai-1) pela ação dos oncogenes E6 e E7 do HPV 16 |
| Beneficiário: | Bruno Belmonte Martinelli Gomes |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |