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 Opportunities: Regular Research Grants
• Start date: August 01, 2019
• End date: August 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Research Foundation - Flanders (FWO)
• Principal Investigator: Bruno Cogliati
• Grantee: Bruno Cogliati
• Principal researcher abroad: Mathieu Frederick Alexander Vinken
• Institution abroad: Vrije Universiteit Brussel (VUB), Belgium
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated 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)

Scientific publications

(10)

(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)

SANTO, SARA GOMES ESPIRITO; DA SILVA, TEREZA CRISTINA; VINKEN, MATHIEU; COGLIATI, BRUNO; BARBISAN, LUIS FERNANDO; ROMUALDO, GUILHERME RIBEIRO. The Implications of Connexin 43 Deficiency during the Early Stages of Chemically Induced Mouse Colon Carcinogenesis. ANTIOXIDANTS, v. 11, n. 12, p. 16-pg., 2022-12-01. (18/10953-9, 22/02175-1)

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. (18/10953-9)

ROMUALDO, GUILHERME RIBEIRO; LEROY, KAAT; COSTA, CICERO JULIO SILVA; PRATA, GABRIEL BACIL; VANDERBORGHT, BART; DA SILVA, TEREZA CRISTINA; BARBISAN, LUIS FERNANDO; ANDRAUS, WELLINGTON; DEVISSCHER, LINDSEY; CAMARA, NIELS OLSEN SARAIVA; et al. In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling. CANCERS, v. 13, n. 21, NOV 2021. (16/14420-0, 16/12015-0, 18/10953-9)

LEROY, KAAT; SILVA COSTA, CICERO JULIO; PIETERS, ALANAH; DOS SANTOS RODRIGUES, BRUNA; VAN CAMPENHOUT, RAF; COOREMAN, AXELLE; TABERNILLA, ANDRES; COGLIATI, BRUNO; VINKEN, MATHIEU. Expression and Functionality of Connexin-Based Channels in Human Liver Cancer Cell Lines. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 22, NOV 2021. (18/10953-9)

LEROY, KAAT; PIETERS, ALANAH; COOREMAN, AXELLE; VAN CAMPENHOUT, RAF; COGLIATI, BRUNO; VINKEN, MATHIEU. Connexin-Based Channel Activity Is Not Specifically Altered by Hepatocarcinogenic Chemicals. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 21, NOV 2021. (18/10953-9)

PIETERS, ALANAH; GIJBELS, EVA; COGLIATI, BRUNO; ANNAERT, PIETER; DEVISSCHER, LINDSEY; VINKEN, MATHIEU. Biomarkers of cholestasis. BIOMARKERS IN MEDICINE, v. 15, n. 6, MAR 2021. (18/10953-9)

COOREMAN, AXELLE; VAN CAMPENHOUT, RAF; YANGUAS, SARA CRESPO; GIJBELS, EVA; LEROY, KAAT; PIETERS, ALANAH; TABERNILLA, ANDRES; VAN BRANTEGEM, PIETER; ANNAERT, PIETER; COGLIATI, BRUNO; et al. Cholestasis Differentially Affects Liver Connexins. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 18, p. 18-pg., 2020-09-01. (18/10953-9, 13/50420-6)

VAN CAMPENHOUT, RAF; COOREMAN, AXELLE; LEROY, KAAT; RUSIECKA, OLGA M.; VAN BRANTEGEM, PIETER; ANNAERT, PIETER; MUYLDERMANS, SERGE; DEVOOGDT, NICK; COGLIATI, BRUNO; KWAK, BRENDA R.; et al. Non-canonical roles of connexins. PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, v. 153, p. 35-41, JUL 2020. (18/10953-9)

VAN CAMPENHOUT, RAF; LEROY, KAAT; COOREMAN, AXELLE; TABERNILLA, ANDRES; COGLIATI, BRUNO; KADAM, PRASHANT; VINKEN, MATHIEU. Connexin-based Channels in the Liver. COMPREHENSIVE PHYSIOLOGY, v. 12, n. 4, p. 17-pg., 2022-10-01. (18/10953-9)

LEROY, KAAT; VILAS-BOASA, VANIA; GIJBELS, EVA; VANDERBORGHT, BART; DEVISSCHER, LINDSEY; COGLIATI, BRUNO; VAN DEN BOSSCHE, BERT; COLLE, ISABELLE; VINKEN, MATHIEU. EXPRESSION OF CONNEXINS AND PANNEXINS IN DISEASED HUMAN LIVER. EXCLI JOURNAL, v. 21, p. 19-pg., 2022-01-01. (18/10953-9)