Involvement of KLK14 in oral carcinoma, through in vitro studies

• Grant number: 22/05582-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2022
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Katiuchia Uzzun Sales
• Grantee: Heloisa Freitas Yamamoto
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Oral cancer is a public health issue and it is a consequence of a few habits i.e., alcoholism and smoking, in addition to pathogens such as HPV. Brazil has one of the highest mortality rates in the world and it is mainly due to late diagnosis of this disease. Proteolytic enzymes, including kallikrein 14 (KLK14), are related to tumor growth and development, as these proteins have a role in several important cellular processes, and gene expression regulation. Indeed, KLK14 is overexpressed in colon and ovary carcinomas, and in hematologic neoplasms. Therefore, we have hypothesized that KLK14 is working towards the oral carcinoma development. Thus, in this study, we aim to knock out KLK14 in oral squamous cell carcinoma cell lines using CRISPR/Cas9 technology. Subsequently, cell migration and proliferation will be evaluated. Finally, KLK14-dependent targets and substrates will be identified using RNA-seq. The experimental strategy detailed in this study will contribute to unveil the KLK14-dependent activation of signaling pathways, in carcinogenesis. Because KLK14 is a secreted protein, it remains as an interesting therapeutic target for future treatments considering that, nowadays, unspecific chemotherapy such as cisplatin is still the first-line treatment for oral squamous cell carcinoma.