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

Abstract：

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 non-malignant 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.

journal_name

Transl Oncol

journal_title

Translational oncology

authors

Alves MG,Kodama MH,da Silva EZM,Gomes BBM,da Silva RAA,Vieira GV,Alves VM,da Fonseca CK,Santana AC,Cecílio NT,Costa MSA,Jamur MC,Oliver C,Cunha TM,Bugge TH,Braz-Silva PH,Colli LM,Sales KU

doi

10.1016/j.tranon.2020.100970

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

100970

issue

1

issn

1936-5233

pii

S1936-5233(20)30462-9

journal_volume

14

pub_type

杂志文章

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