Browsing by Author "Oliveira, Maria José"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Mutant KRAS modulates colorectal cancer cells invasive response to fibroblast-secreted factors through the HGF/C-MET axisPublication . Carvalho, Patrícia Dias; Martins, Flávia; Mendonça, Susana; Ribeiro, Andreia; Machado, Ana Luísa; Carvalho, Joana; Oliveira, Maria José; Velho, SérgiaGenetic alterations influence the malignant potential of cancer cells, and so does thetumor microenvironment. Herein, we combined the study of KRAS oncogenic effectsin colorectal cancer cells with the influence of fibroblast-derived factors. Resultsrevealed that mutant KRAS regulates cell fate through both autonomous and nonau-tonomous signaling mechanisms. Specifically, processes such as proliferation andcell-cell aggregation were autonomously controlled by mutant KRAS independentlyof the stimulation with fibroblasts conditioned media. However, cancer cell invasionrevealed to be a KRAS-dependent nonautonomous effect, resulting from the cooper-ation between fibroblast-derived HGF and mutant KRAS regulation of C-METexpression. C-MET downregulation upon KRAS silencing rendered cells less respon-sive to HGF and thus less invasive. Yet, in one cell line, KRAS inhibition triggeredinvasion upon stimulation with fibroblasts conditioned media. Inhibition of PIK3CAoncogene did not promote invasion, thus showing a KRAS-specific effect. Moreover,the invasive capacity also depended on the HGF-C-MET axis. Overall, our studyawards oncogenic KRAS an important role in modulating the response to fibroblast-secreted factors either by promoting or impairing invasion, and depicts the HGF-C-MET axis as a putative therapeutic target to impair the invasive properties of mutantKRAS cancer cells.
- Overexpression of tumour-associated carbohydrate antigen sialyl-Tn in advanced bladder tumoursPublication . Ferreira, José Alexandre; Videira, Paula; Lima, Luís; Pereira, Sofia; Silva, Mariana; Carrascal, Milene; Severino, Paulo; Fernandes, Elisabete; Almeida, Andreia; Costa, Céu; Vitorino, Rui; Amaro, Teresina; Oliveira, Maria José; Reis, Celso; Dall'Olio, Fabio; Amado, Francisco; Santos, LúcioLittle is known on the expression of the tumour-associated carbohydrate antigen sialyl-Tn (STn), in bladder cancer. We report here that 75% of the high-grade bladder tumours, presenting elevated proliferation rates and high risk of recurrence/progression expressed STn. However, it was mainly found in non-proliferative areas of the tumour, namely in cells invading the basal and muscle layers. STn was also found in tumour-adjacent mucosa, which suggests its dependence on a field effect of the tumour. Furthermore, it was not expressed by the normal urothelium, demonstrating the cancer-specific nature of this antigen. STn expression correlated with that of sialyltransferase ST6GalNAc.I, its major biosynthetic enzyme. The stable expression of ST6GalNAc.I in the bladder cancer cell line MCR induced STn expression and a concomitant increase of cell motility and invasive capability. Altogether, these results indicate for the first time a link between STn expression and malignancy in bladder cancer. Hence, therapies targeting STn may constitute new treatment approaches for these tumours.