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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Relative expression of KLK5 to LEKTI is associated with aggressiveness of oral squamous cell carcinoma

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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]
Total Authors: 18
[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
Total Affiliations: 6
Document type: Journal article
Source: TRANSLATIONAL ONCOLOGY; v. 14, n. 1 JAN 2021.
Web of Science Citations: 0

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)

FAPESP's process: 16/16715-7 - Regulation of hepatocyte growth factor activator inhibitor-1 (HAI-1) activity by HPV 16 oncogenes E6 and E7
Grantee:Bruno Belmonte Martinelli Gomes
Support type: Scholarships in Brazil - Master
FAPESP's process: 16/13228-8 - Genetic study of LEKTI superexpression in HNSCC mouse model
Grantee:Elaine Zayas Marcelino da Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/06316-2 - Genetic epistasis analysis of matriptase-depedent proteolytic pathway in head and neck cancer
Grantee:Katiuchia Uzzun Sales
Support type: Research Grants - Young Investigators Grants