Regulation of hepatocyte growth factor activator inhibitor-1 (HAI-1) activity by HPV 16 oncogenes E6 and E7

• Grant number: 16/16715-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2016
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Katiuchia Uzzun Sales
• Grantee: Bruno Belmonte Martinelli Gomes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/06316-2 - Genetic epistasis analysis of matriptase-depedent proteolytic pathway in head and neck cancer, AP.JP

Abstract

The Head and Neck Squamous Cell Carcinomas (HNSCC) are a heterogeneous group of tumours, consisted of oropharynx cancers, oral cavity cancers, nasal cavity cancers, lip, pharynx, and larynx cancers. The HNSCC appear as the sixth most recurrent type of cancer in the world, with about 550,000 new cases and 300,000 deaths per year. Studies focused on this kind of cancer are imperative because patients affected with HNSCC present relatively low survival rates, mostly due to the absence of specific markers and poor response to available treatments. Given the high mortality and morbidity rates related to the disease, a deeper study on the molecular basis of HNSCC progression is of great importance.Tobacco use and chronic alcohol consumption figure as the main causes of HNSCC. Besides that, there has been an increase in the number of cases related to Human papillomavirus (HPV) infection. Formerly associated with genital cancer, HPV's oncogenic potential relies on the expression of its oncogenes on the genome of infected cells. The E6 and E7 proteins inactivate, respectively, the p53 and pRB (retinoblastoma protein), products of tumour suppressor genes that act in the control of cell stability. The oncogenic effects of HPV also deregulate the expression of groups of proteases related to cell malignant transformation.In the present study, we aim to point, by in vitro biology and animal experimentation, the probable connection between HPV infection and the action of Hai-1 (Hepatocyte Growth Factor Activator Inhibitor-1), an inhibitor of Trypsin-like serine proteases, such as Matriptase, Prostasin and the Hepatocyte Growth Factor, each having a role in tumour development. Several studies indicate that abnormalities on Hai-1 expression are related to different patterns of cancer progression. In addition, previous experiments of our group indicate a possible protective action of inhibitor in the context of HPV infection. Therefore, the detailed understanding of tumorigenic pathways affected by HPV could direct to new therapeutic targets for HNSCC. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALVES, MARCIA GAIAO; KODAMA, MARCIO HIDEKI; MARCELINO DA SILVA, ELAINE ZAYAS; MARTINELLI GOMES, BRUNO BELMONTE; ALVES DA SILVA, RODRIGO ALBERTO; VIEIRA, GABRIEL VILIOD; ALVES, VANI MARIA; DA FONSECA, CAROL KOBORI; SANTANA, ANA CAROLINA; CECILIO, NERRY TATIANA; et al. Relative expression of KLK5 to LEKTI is associated with aggressiveness of oral squamous cell carcinoma. TRANSLATIONAL ONCOLOGY, v. 14, n. 1, JAN 2021. (14/06316-2, 16/13228-8, 16/16715-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

GOMES, Bruno Belmonte Martinelli. Modulation of HPV-dependent phenotype by HAI-1 expression in epithelial stem cells. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.