Cancers, Vol. 13, Pages 4395: Kallikrein 5 Inhibition by the Lympho-Epithelial Kazal-Type Related Inhibitor Hinders Matriptase-Dependent Carcinogenesis

Cancers, Vol. 13, Pages 4395: Kallikrein 5 Inhibition by the Lympho-Epithelial Kazal-Type Related Inhibitor Hinders Matriptase-Dependent Carcinogenesis Cancers doi: 10.3390/cancers13174395 Authors: Elaine Zayas Marcelino da Silva Thais Fernanda de Campos Fraga-Silva Yao Yuan Márcia Gaião Alves Gabriel Azevedo Publio Carol Kobori da Fonseca Márcio Hideki Kodama Gabriel Viliod Vieira Marina Ferreira Candido Lara Maria Alencar Ramos Innocentini Mateus Gonçalves Miranda Alfredo Ribeiro da Silva Jose Carlos Alves-Filho Vania Luiza Deperon Bonato Ramiro Iglesias-Bartolome Katiuchia Uzzun Sales Head and neck squamous cell carcinoma remains challenging to treat with no improvement in survival rates over the past 50 years. Thus, there is an urgent need to discover more reliable therapeutic targets and biomarkers for HNSCC. Matriptase, a type-II transmembrane serine protease, induces malignant transformation in epithelial stem cells through proteolytic activation of pro-HGF and PAR-2, triggering PI3K-AKT-mTOR and NFKB signaling. The serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI) inhibits the matriptase-driven proteolytic pathway, directly blocking kallikreins in epithelial differentiation. Hence, we hypothesized LEKTI could inhibit matriptase-dependent squamous cell carcinogenesis, thus implicating kallikreins in this process. Double-transgenic mice with simultaneous expression of matriptase and LEKTI under the...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research