



@article {3324,
	title = {DNAJB4 molecular chaperone distinguishes WT from mutant E-cadherin, determining their fate in vitro and in vivo},
	journal = {Human Molecular Genetics},
	volume = {23},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {2094 - 2105},
	abstract = {E-cadherin (Ecad) is a well-known invasion suppressor and its loss of expression is common in invasive carcinomas. Germline Ecad mutations are the only known genetic cause of hereditary diffuse gastric cancer (HDGC), demonstrating the causative role of Ecad impairment in gastric cancer. HDGC-associated Ecad missense mutations can lead to folding defects and premature proteasome-dependent endoplasmic reticulum-associated degradation (ERAD), but the molecular determinants for this fate were unidentified. Using a Drosophilabased genetic screen, we found that Drosophila DnaJ-1 interacts with wild type (WT) and mutant human Ecad in vivo. DnaJ (Hsp40) homolog, subfamily B, member 4 (DNAJB4), the human homolog of DnaJ-1, influences Ecad localization and stability even in the absence of Ecad endogenous promoter, suggesting a post-transcriptional level of regulation. Increased expression of DNAJB4 leads to stabilization of WT Ecad in the plasma membrane, while it induces premature degradation of unfolded HDGC mutants in the proteasome. The interaction between DNAJB4 and Ecad is direct, and is increased in the context of the unfolded mutant E757K, especially when proteasome degradation is inhibited, suggesting that DNAJB4 is a molecular mediator of ERAD. Post-translational regulation of native Ecad by DNAJB4 molecular chaperone is sufficient to influence cell adhesion in vitro. Using a chick embryo chorioallantoic membrane assay with gastric cancer derived cells, we demonstrate that DNAJB4 stimulates the anti-invasive function of WT Ecad in vivo. Additionally, the expression of DNAJB4 and Ecad is concomitantly decreased in human gastric carcinomas. Altogether, we demonstrate that DNAJB4 is a sensor of Ecad structural features that might contribute to gastric cancer progression. {\textcopyright} The Author 2013. Published by Oxford University Press. All rights reserved.},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84897831766\&partnerID=40\&md5=c7651a5372b8a46de1f028888590b3f3},
	author = {Sim{\~o}es-Correia, J. and Silva, D.I. and Melo, S. and Figueiredo, J. and Caldeira, J. and Pinto, M.T. and Gir{\~a}o, H. and Pereira, P. and Seruca, R.}
}
@article {3270,
	title = {Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y 1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity},
	journal = {Oncogene},
	volume = {33},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	pages = {2123 - 2133},
	abstract = {The interactions between cancer cells and their microenvironment are crucial for malignant progression, as they modulate invasion-related activities. Tumor-associated macrophages are generally considered allies in the process of tumor progression in several types of cancer, although their role on gastric and colorectal carcinomas is still poorly understood. In this report, we studied the influence of primary human macrophages on gastric and colorectal cancer cells, considering invasion, motility/migration, proteolysis and activated intracellular signaling pathways. We demonstrated that macrophages stimulate cancer cell invasion, motility and migration, and that these effects depend on matrix metalloproteinase (MMP) activity and on the activation of epidermal growth factor receptor (EGFR) (at the residue Y 1086), PLC-γ (phospholipase C-gamma) and Gab1 (GRB2-associated binding protein-1), as evidenced by siRNA (small interference RNA) experiments. Epidermal growth factor (EGF)-immunodepletion impaired macrophage-mediated cancer cell invasion and motility, suggesting that EGF is the pro-invasive and pro-motile factor produced by macrophages. Macrophages also induced gastric and colorectal cancer cell phosphorylation of Akt, c-Src and ERK1/2, and led to an increase of RhoA and Cdc42 activity. Interestingly, whereas macrophage-mediated cancer cell c-Src and ERK1/2 phosphorylation occurred downstream EGFR activation, Akt phosphorylation seems to be a parallel event, taking place in an EGFR-independent manner. The involvement of EGF, EGFR-downstream signaling partners and MMPs in macrophage-mediated invasion provides novel insights into the molecular crosstalk established between cancer cells and macrophages, opening new perspectives for the design of new and more efficient therapeutic strategies to counteract cancer cell invasion. {\textcopyright} 2014 Macmillan Publishers Limited.},
	keywords = {cancer cell invasion, colon cancer, Gastric cancer, invasion-related signaling pathways, Macrophages, tumor microenvironment},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899425243\&partnerID=40\&md5=beff5192ff42940c75fef8b48ebd3ae7},
	author = {Cardoso, A.P. and Pinto, M.L. and Pinto, A.T. and Oliveira, M.I. and Pinto, M.T. and Gon{\c c}alves, R. and Relvas, J.B. and Figueiredo, C. and Seruca, R. and Mantovani, A. and Mareel, M. and Barbosa, M.A. and Oliveira, M.J.}
}
@article {2859,
	title = {Expression of ST3GAL4 Leads to SLex Expression and Induces c-Met Activation and an Invasive Phenotype in Gastric Carcinoma Cells},
	journal = {PLoS ONE},
	volume = {8},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: ScopusArt. No.: e66737},
	month = {2013///},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879165131\&partnerID=40\&md5=58617c0600b708de7a68556b87336112},
	author = {Gomes, C. and Os{\'o}rio, H. and Pinto, M.T. and Campos, D. and Oliveira, M.J. and Reis, C.A.}
}
@booklet {2867,
	title = {Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity},
	howpublished = {Oncogene},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: ScopusArticle in Press},
	month = {2013///},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876908646\&partnerID=40\&md5=bcc2929bb93817db3dc0e3421c420722},
	author = {Cardoso, A.P. and Pinto, M.L. and Pinto, A.T. and Oliveira, M.I. and Pinto, M.T. and Gon{\c c}alves, R. and Relvas, J.B. and Figueiredo, C. and Seruca, R. and Mantovani, A. and Mareel, M. and Barbosa, M.A. and Oliveira, M.J.}
}
