17 documents found, page 1 of 2
The ECM and tissue architecture are major determinants of early invasion mediat...
Melo, Soraia; Guerrero, Pilar; Soares, Maurício Moreira; Bordin, José Rafael; Carneiro, Fátima; Carneiro, Patrícia; Dias, Maria Beatriz; Carvalho, JoãoGermline mutations of E-cadherin cause Hereditary Diffuse Gastric Cancer (HDGC), a highly invasive cancer syndrome characterised by the occurrence of diffuse-type gastric carcinoma and lobular breast cancer. In this disease, E-cadherin-defective cells are detected invading the adjacent stroma since very early stages. Although E-cadherin loss is well established as a triggering event, other determinants of the i...
Targeting the Tumor Microenvironment: An Unexplored Strategy for Mutant KRAS Tu...
Dias Carvalho, Patrícia; Machado, Ana Luísa; Martins, Flávia; Seruca, Raquel; VELHO, SERGIACurrent evidence strongly suggests that cancer cells depend on the microenvironment in order to thrive. In fact, signals from the surrounding tumor microenvironment are crucial for cancer cells´ aggressiveness, altering their expression profile and favoring their metastatic potential. As such, targeting the tumor microenvironment to impair cancer progression became an attractive therapeutic option. Interestingl...
SRC inhibition prevents P-cadherin mediated signaling and function in basallike...
Ribeiro, Ana Sofia; Nobre, Ana Rita; Mendes, Nuno; Almeida, João; Vieira, André Filipe; Sousa, Bárbara; Carvalho, Filomena Almeida; Monteiro, JoanaBACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the trea...
Colorectal cancer-related mutant KRAS alleles function as positive regulators o...
Alves, Sara; Castro, Lisandra; Fernandes, Maria Sofia; Francisco, Rita; Castro, Paula; Priault, Muriel; Chaves, Susana Rodrigues; Moyer, Mary PatThe recent interest to modulate autophagy in cancer therapy has been hampered by the dual roles of this conserved catabolic process in cancer, highlighting the need for tailored approaches. Since RAS isoforms have been implicated in autophagy regulation and mutation of the KRAS oncogene is highly frequent in colorectal cancer (CRC), we questioned whether/how mutant KRAS alleles regulate autophagy in CRC and its...
High-throughput molecular profiling of a P-cadherin overexpressing breast cance...
Bernardes, Nuno; Ribeiro, Ana Sofia; Abreu, Sofia; Vieira, André F.; Carreto, Laura; Santos, Manuel; Seruca, Raquel; Paredes, Joana; Fialho, Arsenio M.Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells. We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression...
P-cadherin functional role is dependent on E-cadherin cellular context: a proof...
Ribeiro, Ana Sofia; Sousa, Bárbara; Carreto, Laura; Mendes, Nuno; Nobre, Ana Rita; Ricardo, Sara; Albergaria, André; Cameselle-Teijeiro, Jorge F.P-cadherin overexpression is associated with worse breast cancer survival, being a poor prognostic marker as well as a putative therapeutic target for the aggressive triple-negative and basal-like carcinomas (TNBCs). Previously, we have shown that P-cadherin promotes breast cancer invasion of cells where membrane E-cadherin was maintained; however, it suppresses invasion in models without endogenous cadherins, ...
E-cadherin destabilization accounts for the pathogenicity of missense mutations...
Simões-Correia, Joana; Figueiredo, Joana; Lopes, Rui; Stricher, François; Oliveira, Carla; Serrano, Luís; Seruca, RaquelE-cadherin is critical for the maintenance of tissue architecture due to its role in cell-cell adhesion. E-cadherin mutations are the genetic cause of Hereditary Diffuse Gastric Cancer (HDGC) and missense mutations represent a clinical burden, due to the uncertainty of their pathogenic role. In vitro and in vivo, most mutations lead to loss-of-function, although the causal factor is unknown for the majority. We...
Transcription initiation arising from E-cadherin/CDH1 intron2: a novel protein ...
Pinheiro, Hugo; Carvalho, Joana; Oliveira, Patrícia; Ferreira, Daniel; Teixeira Pinto, Marta; Osório, Hugo; Licastro, Danilo; Bordeira-Carriço, RenataDisruption of E-cadherin (CDH1 gene) expression, subcellular localization or function arises during initiation and progression of almost 90% of all epithelial carcinomas. Nevertheless, the mechanisms through which this occurs are largely unknown. Previous studies showed the importance of CDH1 intron 2 sequences for proper gene and protein expression, supporting these as E-cadherin cis-modulators. Through RACE a...
Docosahexaenoic acid inhibits Helicobacter pylori growth in vitro and mice gast...
Correia, Marta; Michel, Valérie; Matos, António A.; Carvalho, Patrícia; Oliveira, Maria J.; Ferreira, Rui M.; Dillies, Marie-Agnès; Huerre, MichelH. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA) to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST) in combination wit...
Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-...
Carvalho, Joana; van Grieken, Nicole C.; Pereira, Patrícia M.; Sousa, Sónia; Tijssen, Marianne; Buffart, Tineke E.; Diosdado, Begoña; Grabsch, HeikeE-cadherin expression disruption is commonly observed in metastatic epithelial cancers and is a crucial step in gastric cancer (GC) initiation and progression. As aberrant expression of microRNAs often perturb the normal expression/function of pivotal cancer-related genes, we characterized and dissected a pathway that causes E-cadherin dysfunction via loss of microRNA-101 and up-regulation of EZH2 expression in...