THE ROLE OF RECK PROTEIN IN HUMAN PAPILLOMAVIRUS MEDIATED CARCINOGENESIS

• Grant number: 13/27006-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2014
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Enrique Mario Boccardo Pierulivo
• Grantee: Suellen da Silva Gomes Herbster
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Persistent infection with high-risk Human Papillomavirus (HPV) types is the main risk factor for the development of cervical cancer. The HPV carcinogenic mechanisms include alterations in extracellular matrix (ECM) components, as matrix metalloproteinases (MMP) and its regulators. These proteins play a central role in many physiological processes and diseases such as homeostatic tissue remodeling and cancer. The REversion-inducing Cysteine-rich protein with Kazal motifs (RECK) plays a central role on tissue remodeling, tumor angiogenesis and can exert inhibitory effects on the transcription, synthesis, activation and activity of MMP-2, MMP-9 e MMP-14 (MT1-MMP). As previously published by our group, it has been observed a correlation between the HPV16 E7 oncoprotein expression, the up-regulation of MMP-9 and the down-regulation of its inhibitors, RECK and tissue inhibitor of metalloproteinases 2 (TIMP-2). Also, RECK expression was observed in higher levels in cervicitis samples than in CINII/III and invasive carcinoma samples indicating that RECK down-regulation may correlate with lesion grade. Therefore, we suggest that RECK down-regulation may be important in the natural history of cervical cancer. The present study aims to understand the role of RECK in HPV mediated carcinogenesis. In order to do this, we will assess the effects of RECK superexpression in the tumorigenic potential of cervical tumors derived cell lines. Thus, we will evaluate its clonogenic, anchorage-independent growth, migration and invasion potentials and its ability to generate tumors in immunodeficient mice when compared to control cells. All together, this study will help to determine if RECK could represent a new biomarker of cervical cancer progression and a potential target for therapy.

Scientific publications

(5)

(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)

HERBSTER, SUELLEN; PALADINO, ANDRESSA; DE FREITAS, SUMARA; BOCCARDO, ENRIQUE. Alterations in the expression and activity of extracellular matrix components in HPV-associated infections and diseases. Clinics, v. 73, n. 1, 2018. (08/57889-1, 13/27006-9)

SUELLEN HERBSTER; ANDRESSA PALADINO; SUMARA DE FREITAS; ENRIQUE BOCCARDO. Alterations in the expression and activity of extracellular matrix components in HPV-associated infections and diseases. Clinics, v. 73, 2018-09-06. (08/57889-1, 13/27006-9)

ABJAUDE, WALASON; PRATI, BRUNA; MUNFORD, VERIDIANA; MONTENEGRO, ALINE; LINO, VANESCA; HERBSTER, SUELLEN; RABACHINI, TATIANA; TERMINI, LARA; MENCK, CARLOS FREDERICO MARTINS; BOCCARDO, ENRIQUE. ATM Pathway Is Essential for HPV-Positive Human Cervical Cancer-Derived Cell Lines Viability and Proliferation. PATHOGENS, v. 11, n. 6, p. 19-pg., 2022-06-01. (17/02997-3, 13/27006-9, 12/16512-8, 10/20002-0, 19/19435-3)

PRATI, BRUNA; ABJAUDE, WALASON DA SILVA; TERMINI, LARA; MORALE, MIRIAN; HERBSTER, SUELLEN; LONGATTO-FILHO, ADHEMAR; LIMA NUNES, RAFAELLA ALMEIDA; CORDOBA CAMACHO, LIZETH CAROLINA; RABELO-SANTOS, SILVIA HELENA; ZEFERINO, LUIZ CARLOS; et al. Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo. SCIENTIFIC REPORTS, v. 9, JAN 23 2019. (08/57889-1, 10/20002-0, 13/27006-9, 12/16512-8, 11/14416-9)

HERBSTER, SUELLEN; TROMBETTA-LIMA, MARINA; DE SOUZA-SANTOS, PAULO THIAGO; PALADINO, ANDRESSA; SILVEIRA, CAIO RAONY FARINA; SOGAYAR, MARI CLEIDE; VILLA, LUISA LINA; LEPIQUE, ANA PAULA; BOCCARDO, ENRIQUE. Low RECK Expression Is Part of the Cervical Carcinogenesis Mechanisms. CANCERS, v. 13, n. 9, MAY 2021. (08/57889-1, 17/02997-3, 10/20002-0, 13/27006-9)

Academic Publications

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

HERBSTER, Suellen da Silva Gomes. The role of RECK super expression in HPV associated tumorigenesis.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.