Where Ideas Grow

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.

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

Team

Adriana Gaspar da Rocha
Clinical Affiliate Member
Miguel Melo
Clinical Affiliate Member
Ana Preto
Collaborator
Catarina Tavares
Collaborator
Rui Batista
Collaborator

Selected Publications

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: 579] [IF: 6,5]
DOI: 10.1038/sj.onc.1206706 SCOPUS: 0043170833

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: 8] [IF: 10,2]
DOI: 10.1016/j.semcancer.2017.06.014 SCOPUS: 85023602451

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: 682] [IF: 10,7]
DOI: 10.1038/ncomms3185 SCOPUS: 84884524540

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

Nunes J.B., Peixoto J., Soares P., Maximo V., Carvalho S., Pinho S.S., Vieira A.F., Paredes J., Rego A.C., Ferreira I.L., Gomez-Lazaro M., Sobrinho-Simoes M., Singh K.K., Lima J.,
OXPHOS dysfunction regulates integrin-ß1 modifications and enhances cell motility and migration. Human Molecular Genetics24(7):1977-1990, 2014. [Journal: Article] [CI: 32] [IF: 6,4]
DOI: 10.1093/hmg/ddu612 SCOPUS: 84926488610

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: 110] [IF: 9,7]
DOI: 10.1073/pnas.1201232109 SCOPUS: 84871862427

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: 98] [IF: 7,2]
DOI: 10.1038/jid.2014.163 SCOPUS: 84904458479

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: 806] [IF: 2]
DOI: 10.1007/s00428-007-0452-1 SCOPUS: 34848828173

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: 46] [IF: 6,5]
DOI: 10.1002/ijc.30057 SCOPUS: 84961644849

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: 67] [IF: 6,4]
DOI: 10.1210/jc.2011-2748 SCOPUS: 84863566153

Ongoing Projects

Programa Mind para doentes oncológicos: Ensaio controlado randomizado para o teste de custo-efetividade e eficácia na mudança de indicadores psicológicos e biológicos em mulheres com carcinoma da mama
Reference: PTDC/PSI-GER/7847/2020
Proponent: Universidade de Coimbra
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-SEP-21 to 31-AUG-25
Ctrl+ALT+Cel: ATRX control in ALT and in the pancreas beta cell
Reference: PTDC/MED-ONC/0531/2021
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 31-DEC-24
Engineered nano-based device for glioblastoma multiforme therapy
Reference: M-ERA-NET3/0002/2021
Proponent: FEUP - Faculdade Engenharia do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JUL-22 to 30-JUN-25
Unravel familial non-medullary thyroid cancer aetiology: A Genetic Orphan Disease
Reference: 2022.05763.PTDC
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-MAR-23 to 31-AUG-24
Implementação de Biomarcadores Moleculares para medicina de precisão com doentes com tumores cerebrais pediátricos
Reference: LEOJL
Proponent: Ipatimup
Sponsor: Liga Portuguesa Contra o Cancro
From 04-SEP-18 to 03-SEP-24
Targeting mitochondrial TERT to overcome therapeutic resistance
Proponent: Ipatimup
Sponsor: ETA
From 15-JUL-20 to 14-JUL-25
Molecular characterisation of corticotroph adenomas in a Portuguese cohort
Proponent: Ipatimup
Sponsor: SPEDM
From 01-JUL-21 to 30-JUN-24
Fishing endocrine disruptors contribution to cancer
Proponent: Ipatimup
Sponsor: SPEDM
From 01-JUL-21 to 30-JUN-24
"Identificação de biomarcadores moleculares de metastização em melanoma cutâneo"
Proponent: Ipatimup
Sponsor: Pierre Fabre Médicament Portugal, Lda
From 01-JAN-22 to 30-DEC-25
Assessing the mitochondrial impact of TERT in thyroid cancer
Proponent: - Ipatimup
Sponsor: SPEDM
From 01-JUL-23 to 31-AUG-25
Caracterização histológica, molecular e proteica dos carcinomas da tireoide avançados, tratados com inibidores de tirosina cinase
Proponent: - Ipatimup
Sponsor: SPEDM
From 01-JUL-23 to 30-JUN-25
Study the relevance of superoxide dismutase 2 in thyroid cancer
Proponent: - Ipatimup
Sponsor: SPEDM
From 01-JUL-23 to 31-AUG-25