Cancer Signalling & Metabolism
ABOUT
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.
RESEARCH
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.
Team
Selected Publications
OXPHOS dysfunction regulates integrin-β1 modifications and enhances cell motility and migration. Human Molecular Genetics24(7):1977-1990, 2014. [Journal: Article] [CI: 33] [IF: 6,4]
DOI: 10.1093/hmg/ddu612 SCOPUS: 84926488610
Pópulo H., Boaventura P., Vinagre J., Batista R., Mendes A., Caldas R., Pardal J., Azevedo F., Honavar M., Guimarães I., Manuel Lopes J., Sobrinho-Simões M., Soares P.
TERT promoter mutations in skin cancer: The effects of sun exposure and X-irradiation. Journal of Investigative Dermatology134(8):2251-2257, 2014. [Journal: Article] [CI: 100] [IF: 7,2]
DOI: 10.1038/jid.2014.163 SCOPUS: 84904458479
Batista R., Cruvinel-Carloni A., Vinagre J., Peixoto J., Catarino T.A., Campanella N.C., Menezes W., Becker A.P., De Almeida G.C., Matsushita M.M., Clara C., Neder L., Viana-Pereira M., Honavar M., Castro L., Lopes J.M., Carvalho B., Vaz R.M., Máximo V., Soares P., Sobrinho-Simões M., Reis R.M., Lima J.
The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism. International Journal of Cancer139(2):414-423, 2016. [Journal: Article] [CI: 50] [IF: 6,5]
DOI: 10.1002/ijc.30057 SCOPUS: 84961644849
Correia M., Pinheiro P., Batista R., Soares P., Sobrinho-Simões M., Máximo V.
Etiopathogenesis of oncocytomas. Seminars in Cancer Biology47:82-94, 2017. [Journal: Review] [CI: 9] [IF: 10,2]
DOI: 10.1016/j.semcancer.2017.06.014 SCOPUS: 85023602451
Boaventura P., Soares P., Pereira D., Teixeira-Gomes J., Sobrinho-Simões M.
Head and neck lesions in a cohort irradiated in childhood for tinea capitis treatment. The Lancet Infectious Diseases11(3):163-164, 2011. [Journal: Letter] [CI: 14] [IF: 17,4]
DOI: 10.1016/S1473-3099(11)70047-0 SCOPUS: 79952026090
Rindi G., Klöppel G., Couvelard A., Komminoth P., Körner M., Lopes J.M., McNicol A.M., Nilsson O., Perren A., Scarpa A., Scoazec J.Y., Wiedenmann B.
TNM staging of midgut and hindgut (neuro) endocrine tumors: A consensus proposal including a grading system. Virchows Archiv451(4):757-762, 2007. [Journal: Article] [CI: 814] [IF: 2]
DOI: 10.1007/s00428-007-0452-1 SCOPUS: 34848828173
Soares P., Trovisco V., Rocha A.S., Lima J., Castro P., Preto A., Máximo V., Botelho T., Seruca R., Sobrinho-Simões M.
BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene22(29):4578-4580, 2003. [Journal: Article] [CI: 583] [IF: 6,5]
DOI: 10.1038/sj.onc.1206706 SCOPUS: 0043170833
Couto J.P., Daly L., Almeida A., Knauf J.A., Fagin J.A., Sobrinho-Simões M., Lima J., Máximo V., Soares P., Lyden D., Bromberg J.F.
STAT3 negatively regulates thyroid tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America109(35):E2361-E2370, 2012. [Journal: Article] [CI: 114] [IF: 9,7]
DOI: 10.1073/pnas.1201232109 SCOPUS: 84871862427
Faustino A., Couto J.P., Pópulo H., Rocha A.S., Pardal F., Cameselle-Teijeiro J.M., Lopes J.M., Sobrinho-Simões M., Soares P.
mTOR pathway overactivation in BRAF mutated papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism97(7):, 2012. [Journal: Article] [CI: 68] [IF: 6,4]
DOI: 10.1210/jc.2011-2748 SCOPUS: 84863566153
Vinagre J., Almeida A., Pópulo H., Batista R., Lyra J., Pinto V., Coelho R., Celestino R., Prazeres H., Lima L., Melo M., Rocha A.G.D., Preto A., Castro P., Castro L., Pardal F., Lopes J.M., Santos L.L., Reis R.M., Cameselle-Teijeiro J., Sobrinho-Simões M., Lima J., Máximo V., Soares P.
Frequency of TERT promoter mutations in human cancers. Nature Communications4:, 2013. [Journal: Article] [CI: 693] [IF: 10,7]
DOI: 10.1038/ncomms3185 SCOPUS: 84884524540