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Are connexins, pannexins and their (hemi)channels novel biomarkers and pharmacological targets in the prognosis and therapy of liver cancer?

Grant number: 18/10953-9
Support type:Regular Research Grants
Duration: August 01, 2019 - July 31, 2022
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Cooperation agreement: Research Foundation - Flanders (FWO)
Principal researcher:Bruno Cogliati
Grantee:Bruno Cogliati
Principal researcher abroad: Mathieu Frederick Alexander Vinken
Institution abroad: Vrije Universiteit Brussel (VUB), Belgium
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Luís Fernando Barbisan ; Thiago Pinheiro Arrais Aloia ; Wellington Andraus

Abstract

Connexin and pannexin proteins are the building stones of hemichannels and channels, respectively, which are transmembrane pores that mediate paracrine cellular communication, in particular in pathological conditions. Belgian-Brazilian joint research over the past years showed altered expression of connexin43 and pannexin1 in acute and chronic liver disease as well as alleviation of the clinical manifestation of liver pathology upon pharmacological inhibition of their (hemi)channels. These findings suggest that connexins, pannexins and their (hemi)channels can serve as biomarkers and therapeutic targets in the hepatology field. The present Belgian-Brazilian project will investigate whether these findings can be extrapolated to liver cancer, which frequently is the end stage of chronic liver disease. Animal and cell culture models of liver cancer will be studied for expression of connexin43 and pannexin1. This will be complemented by testing of human liver cancer samples and linked to disease progression. Subsequently, connexin43 and pannexin1 (hemi)channels will be pharmacologically inhibited in the animal and cell culture models, whether or not together with established liver cancer therapeutics, followed by investigation of clinical features of liver cancer. Overall, this project, by combining fundamental with translational research, is considered of clinical relevance, as it may introduce a novel strategy for the prognosis and treatment of liver cancer. (AU)

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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)
VAN CAMPENHOUT, RAF; COOREMAN, AXELLE; LEROY, KAAT; RUSIECKA, OLGA M.; VAN BRANTEGEM, PIETER; ANNAERT, PIETER; MUYLDERMANS, SERGE; DEVOOGDT, NICK; COGLIATI, BRUNO; KWAK, BRENDA R.; VINKEN, MATHIEU. Non-canonical roles of connexins. PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, v. 153, p. 35-41, JUL 2020. Web of Science Citations: 0.
LEROY, KAAT; PIETERS, ALANAH; TABERNILLA, ANDRES; COOREMAN, AXELLE; VAN CAMPENHOUT, RAF; COGLIATI, BRUNO; VINKEN, MATHIEU. Targeting gap junctional intercellular communication by hepatocarcinogenic compounds. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS, v. 23, n. 6 JUN 2020. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.