Portal de investigação
Integrin ß1 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Ferreira, RM
- Xu, H
- Gonçalves, M
- Barros-Carvalho, A
- Cravo, J
- Maia, AF
- Carneiro, P
- Smith, ML
- Stamenovic, D
- Morais-de-Sá, E
- Seruca, R
Unidades de investigação
Abstract
Background Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell-cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM). Methods To identify ECM components and receptors relevant for adhesion of E-cadherin dysfunctional cells, we implemented a novel ECM microarray platform coupled with molecular interaction networks. The functional role of putative candidates was determined by combining micropattern traction microscopy, protein modulation and in vivo approaches, as well as transcriptomic data of 262 gastric carcinoma samples, retrieved from the cancer genome atlas (TCGA). Results Here, we show that E-cadherin mutations induce an abnormal interplay of cells with specific components of the ECM, which encompasses increased traction forces and Integrin beta 1 activation. Integrin beta 1 synergizes with E-cadherin dysfunction, promoting cell scattering and invasion. The significance of the E-cadherin-Integrin beta 1 crosstalk was validated in Drosophila models and found to be consistent with evidence from human gastric carcinomas, where increased tumour grade and poor survival are associated with low E-cadherin and high Integrin beta 1 levels. Conclusions Integrin beta 1 is a key mediator of invasion in carcinomas with E-cadherin impairment and should be regarded as a biomarker of poor prognosis in gastric cancer.
Dados da publicação
- ISSN/ISSNe:
- 1436-3291, 1436-3305
- Tipo:
- Article
- Páginas:
- 124-137
- Link para outro recurso:
- www.scopus.com
Gastric Cancer Springer Japan
Citações Recebidas na Web of Science: 11
Citações Recebidas na Scopus: 18
Documentos
- Não há documentos
Filiações
Keywords
- E-cadherin; Hereditary diffuse gastric cancer; Extracellular matrix; Invasion; Integrin beta 1
Financiamento
Proyectos asociados
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Investigador Principal: Maria do Céu Fontes Herdeiro Figueiredo
Estudo Clínico Académico (Helicobacter) . 2019
Immune checkpoint inhibitors for the treatment of gastric cancer
Investigador Principal: Maria do Céu Fontes Herdeiro Figueiredo
Estudo Clínico Académico . 2021
Evaluation of the use of Helicobacter pylori genotypes and gastric microbiota markers to identify individuals at high risk of gastric carcinoma
Investigador Principal: Maria do Céu Fontes Herdeiro Figueiredo
Estudo Clínico Académico . 2021
Citar a publicação
Figueiredo J,Ferreira RM,Xu H,Gonçalves M,Barros A,Cravo J,Maia AF,Carneiro P,Figueiredo C,Smith ML,Stamenovic D,Morais E,Seruca R. Integrin ß1 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells. Gastric Cancer. 2022. 25. (1):p. 124-137. IF:7,400. (1).
