Microbes & Cancer

Our long-term goal is to understand the pathogenesis of cancers mediated by microbial agents, and to contribute knowledge to develop improved strategies for prevention and early diagnosis of cancer, based on the properties of the microbes.

In the last years, we have successfully been using Helicobacter pylori infection and gastric cancer as a study model of microbe-associated cancer. Our results have contributed to the current view that progression towards cancer depends on the combined effects of host susceptibility and bacterial virulence factors. We have shown that infection with specific H. pylori virulence-associated genotypes increases the levels of gastric inflammation and epithelial damage, and the risk for gastric atrophy, intestinal metaplasia, and gastric cancer. We have also identified the bacterial virulence factors and the host cell signalling pathways involved in H. pylori-mediated alterations in cell-cell adhesion and cell invasion. More recently, we have been exploring the relationship between the gastric microbiome and gastric carcinogenesis.

Our research relies on well-characterized patient cohorts, in vitro and in vivo models of infection and cancer, allied to microbiology, molecular and cellular biology, next-generation sequencing, and bioinformatics.



Selected publications


1.       Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, Costa JL, Carneiro F, Machado JC, Figueiredo C. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut 67:226-236, 2018.

2.       Pereira-Marques J, Ferreira RM, Pinto-Ribeiro I, Figueiredo C. Helicobacter pylori Infection, the Gastric Microbiome and Gastric Cancer. Advances in Experimental Medicine and Biology doi: 10.1007/5584_2019_366, 2019.

3.       Pereira-Marques J, Hout A, Ferreira RM, Weber M, Pinto-Ribeiro I, van Doorn LJ, Knetsch CW, Figueiredo C. Impact of Host DNA and Sequencing Depth on the Taxonomic Resolution of Whole Metagenome Sequencing for Microbiome Analysis. Frontiers in Microbiology 10:1277, 2019.

4.       Marques MS, Melo J, Cavadas B, Mendes N, Pereira L, Carneiro F, Figueiredo C*, Leite M*. Afadin downregulation by Helicobacter pylori induces epithelial to mesenchymal transition in gastric cells. Frontiers in Microbiology 9:2712, 2018.

5.       Figueiredo C, Camargo MC, Leite M, Fuentes-Pananá EM, Rabkin CS, Machado JC. Pathogenesis of Gastric Cancer: Genetics and Molecular Classification. Current Topics in Microbiology and Immunology 400:277-304, 2017.

6.       Ferreira RM, Pinto-Ribeiro I, Wen X, Marcos-Pinto R, Dinis-Ribeiro M, Carneiro F, Figueiredo C. Helicobacter pylori cagA promoter region sequences influence CagA expression and interleukin-8 secretion. Journal of Infectious Diseases 213: 669-73, 2016.

7.       Costa AM, Ferreira RM, Pinto-Ribeiro I, Sougleri IS, Oliveira MJ, Carreto L, Santos MA, Sgouras DN, Carneiro F, Leite M, Figueiredo C. Helicobacter pylori activates matrix metalloproteinase-10 in gastric epithelial cells via EGFR and ERK-mediated pathways. Journal of Infectious Diseases 213:1767-76, 2016.

8.       Gonzalez CA*, Figueiredo C*, Bonet C, Ferreira RM, Pardo ML, Ruiz Liso JM, Alonso P, Sala N, Capella G, Sanz-Anquela JM. Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: a long term follow up in a high-risk area in Spain. American Journal of Gastroenterology 106:867-74, 2011.

9.       Machado AM, Figueiredo C, Seruca R, Rasmussen LJ. Helicobacter pylori infection generates genetic instability in gastric cells. BBA - Reviews on Cancer 1806: 58-65, 2010.

10.    Oliveira MJ, Costa AM, Costa AC, Ferreira RM, Sampaio P, Machado JC, Seruca R, Mareel M, Figueiredo C. CagA Associates with c-Met, E-Cadherin, and p120-Catenin in a Multiproteic Complex That Suppresses Helicobacter pylori-Induced Cell-Invasive Phenotype. Journal of Infectious Diseases 200:745-55, 2009.

11.    Machado AM*, Figueiredo C*, Touati E, Máximo V, Sousa S, Michel V, Carneiro F, Nielsen FC, Seruca R, Rasmussen LJ. Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells. Clinical Cancer Research 15:2995-3002, 2009.

12.    Oliveira MJ, Costa AC, Costa AM, Henriques L, Suriano G, Atherton JC, Machado JC, Carneiro F, Seruca R, Mareel M, Leroy A, Figueiredo C. Helicobacter pylori induces gastric epithelial cell invasion in a c-Met and type IV secretion system dependent manner. Journal of Biological Chemistry 281: 34888-34896, 2006

13.    Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, Alves CC, Campos ML, van Doorn LJ, Caldas C, Seruca R, Carneiro F, Sobrinho-Simões M. A pro-inflammatory genetic profile increases the risk of chronic atrophic gastritis and gastric carcinoma. Gastroenterology 125: 364-371, 2003.

14.    Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simões M. Helicobacter pylori and interleukin-1 genotyping: An opportunity to identify high-risk individuals for gastric carcinoma. Journal of the National Cancer Institute 94: 1680-1687, 2002.

15.    Nogueira C*, Figueiredo C*, Carneiro F, Taveira-Gomes A, Barreira R, Figueira P, Salgado C, Belo L, Peixoto A, Bravo JC, Bravo LE, Realpe JL, Plaisier AP, Quint WG, Ruiz B, Correa P, van Doorn LJ. Helicobacter pylori genotypes may determine gastric histopathology. American Journal of Pathology 158: 647-654, 2001.

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