Where Ideas grow

Cancer Signalling & Metabolism


The group aims to identify molecular mechanisms involved in human cancer development with potential applications in the diagnosis, prognosis and targeted therapy, using as models thyroid and other neuroendocrine tumors. Besides the component of translational research, the group has basic research interests such as oncogenic signaling, survival mechanisms and mechanisms/molecules involved in mobility and invasion. Within this frame, a particular attention is paid to: a) signalling induced by genetic alterations in tyrosine kinase receptors and signal transducing molecules involved in the MAPK  and the PI3K/mTOR pathway; b) survival mechanisms of cancer cells, including telomerase reactivation and apoptosis dysregulation; c) molecular mechanisms of metabolic alterations secondary to mitochondrial DNA mutations/deletions or to mutations in nuclear genes encoding metabolic enzymes.



In 2003, we identified BRAFV600E mutation as a major oncogenic event in papillary thyroid carcinoma. Since then the group has been focusing on the genetic alterations underlying genotypic-phenotypic correlations and in the signaling of oncogenic activation in thyroid tumors. This line of research is still being pursued through the study of thyroid tumors as well as other tumor types characterized by a high prevalence of BRAF mutations (nevi and melanoma), using in vitro and in vivo models to progress in the understanding of the BRAF-induced cellular effects. We also addressed the etiopathogenesis of familial forms of thyroid cancer, namely medullary thyroid carcinoma. In close collaboration with clinicians we have been collecting families with thyroid cancer aggregation. Regarding the effect of environmental factors in thyroid carcinogenesis we have been following-up a cohort of individuals that suffered, 50 to 60 years ago, epilation by scalp X-ray irradiation for Tinea capitis treatment. We verified that mtDNA large deletions are a hallmark of Hurthle cell tumours. The results obtained in the field of mitochondrion-rich tumors were the starting point for the study of mitochondrial and metabolic dysfunction in cancer, a sub-area in which our group is using several models other than thyroid tumors.

One of our group interests is to understand telomere maintenance mechanisms. We have unveiled TERT promoter mutations in thyroid cancer as a mechanism for telomere elongation. In the figure, we present interphase and metaphase spreads (blue) of a thyroid cancer cell line, K1, where we can observe by