Patologia Molecular Translacional

Nuestro grupo pretende elucidar los mecanismos moleculares implicados en la progresión tumoral hasta sus metástasis con el fin de identificar nuevos marcadores diagnósticos, pronósticos así como nuevas dianas terapéuticas. Gracias al profundo conocimiento en las bases moleculares tumorales del grupo de investigación, así como la disponibilidad de muestras tumorales humanas, desarrollamos diferentes líneas de investigación centradas en:

Conocer los mecanismos moleculares que subyacen de la cooperación clonal así como la comunicación intercelular implicadas en la heterogeneidad tumoral.
Describir el papel de las MNKs en el desarrollo de resistencias frente al estrés celular.
Ahondar en el papel de ITGB3 en la comunicación intercelular mediada por vesículas extracelulares en modelos de metástasis (Santiago Ramón y Cajal).
Estudiar de las comunicaciones célula-célula mediante uniones intercelulares comunicantes (gap junctions) y/o protrusiones celulares en cáncer (Trond Aasen).
Estudiar de la transformación oncogénica de los Neurofibromas plexiformes (Cleofe Romagosa).

Líneas de investigación

Mechanisms of cerebral aging: role of GSK3ß/cdk5 and sirtuins.

Aging may be considered as an accumulation of changes in cells and tissues that increases the risk of disease and death. The senescence-accelerated prone mice SAMP8 is an aging model with brain histopathological signs and other aging-related disorders, such as ß-amyloid and tau protein aggregates and increased oxidative stress. If hyperphosphorylated, tau protein contributes to the development of a tauopathy, process linked to neurodegenerative diseases of the aging brain such as Alzheimer disease. Several kinases (PKC, ERK, CDK5 or GSK3ß) perform this tau protein post-transcriptional modification. We plan to determine the effect that inhibitors of these kinases such as lithium, in vivo and in vitro, could have in slowing down the brain neurodegenerative processes. Besides, we will study the role of a newly described protein family, sirtuins.

Sirtuins are ontogenically preserved proteins related to longevity. We will evaluate the gene and protein expression of Sirt 1, 2 and 3 in cultured neurons and in the brain of this mouse strain. We seek to elucidate the participation of sirtuins in cerebral ageing using as a tools resveratrol, a flavonoid described as activator of these proteins, and caloric restriction, two paradigms that lead to an elongation of lifespan and neuroprotection in several animal models. In the in vitro studies, the role of GDNF in maintaining neuronal functionality and its correlation with sirtuins will be investigated because this trophic factor decreases with aging and shows a lesser expression in SAMP8 mice. These studies will contribute to the development of new therapeutic strategies to prevent age-related neurodegeneratives diseases.

IP: -

Role of HER3 expression in carcinogenesis of endometrial and breast tumors. Search for new predictive markers to anti-HER treatments.

The cell signaling pathways downstream of epidermal growth factor receptor family members is tightly regulated in normal epithelial cells, and its alteration induce different cell processes (cell proliferation, cell growth, etc...) which triggers in cellular transformation. Within this family receptors, HER1/EGFR and HER2/neu are the best known, being subject to interest other family members like HER3. The aim of the study is establish de role of HER3 protein expression by Immunohistochemistry in endometrial and breast tumors, and establish any association with clinic-pathological parameters. Furthermore, we would like to know the implication of HER3 in the resistance mechanisms to anti-HER treatment agents.

IP: Javier Hernandez Losa

Study of CAP-dependent and CAP-independent signalling pathways in breast carcinomas.

In previous works we studied several factors involved in cell signalling pathways that control cell growth. The found that the phosphorylated form of 4E-BP1 was the only factor that correlated with prognosis, and histologic aggressive features in several types of cancers. 4E-BP1 is a key regulator of CAP-dependent traslation and its main function is the inactivation of eIF4E. However, not all the aggressive tumors show activation of this factor. On the other hand, it has been shown that under hypoxia conditions cells the translation of some key factors can be regulated by CAP-independent pathways, mediated by factors known as ITAFs. The aim of our study is to find the CAP-depdendent/CAP-independent balance in tumors in relation to hypoxia, and evaluate its impact on prognosis.

IP: Josep Castellví Vives

Study of Cell Signalling pathway in human tumors. Identification of funnel factors. Study of Cell Signalling pathway in human tumors. Identification of funnel factors.

We have characterized the levels of activation in Cell Signalling in a spectrum of solid tumors and correlated the levels of various factors, including mTOR and downstream proteins (p70S6K, S6, 4EBP1, eIF4E) with prognosis and grade of malignancy. Also, are being characterized, at the molecular level, the factors involved in controlling the translation cap dependent and independent in malignant tumors.

IP: Santiago Ramon y Cajal Agüeras