Cancer Metabolism and Microenvironment

Jacinta Serpa

Jacinta Serpa

Principal Investigator
[2006-2010] PostDoc in Instituto Português de Oncologia de Lisboa- Angiogenesis Group; PI-Sérgio Dias.
[2002-2005] PhD in Human Biology in Faculdade de Medicina da Universidade do Porto; Supervisor: Leonor David.
[1992-1997] Graduation in Applied Biology, Universidade dos Açores.



Instituto Português de Oncologia de Lisboa, Francisco Gentil
R. Prof. Lima Basto, 1099-023 Lisboa, Portugal

Phone: (+351) 217 229 800
Fax: (+351) 218 851 920
E-mail: jacinta.serpa(at)

Main Interests:

Metabolism is undoubtedly one of the currently rediscovered fields of research and it will certainly be a niche of scientific discoveries that will allow the evolution of the knowledge and treatment of diseases, namely cancer. The metabolic adaptation of cancer cells not only permits the development and establishment of a tumor, in a certain microenvironment, but it also conditions the response to the therapy.
Metabolic adaptation cannot be assessed exclusively from the cancer cell point of view but should as well consider the contribution of stromal (non-cancerous) cells in the same tissue or organ. Metabolism does not consist solely of the intracellular network that shares and provides organic compounds among the various chemical reactions that make up the metabolic dynamics, but also encompasses the extracellular organic and signaling molecules that supplement and mediate stimuli, which regulate the entire metabolic functioning of a cell. In cancer, the surrounding cells (fibroblasts, endothelial cells, immune cells and adipocytes) influence the tumor microenvironment, the tumor cell biology and metabolism.
The main research area of CMM group is cancer metabolism not only the metabolic adaptive features that allow the establishment of a tumor in a certain microenvironment but also the way these metabolic adaptations limit the response to therapy.

Our projects assess the role of cancer metabolism in different in vitro and in vivo cancer models as leukemia, lung, breast, colon, uterine cervix and ovarian cancer.
Our studies have already consolidated the role of transporters as mediators of the uptake of cytotoxic compounds, as monocarboxylate transporter 1 (MCT1) in uterine cervix cancer (Silva et al., 2016) and in acute myeloid leukemia (Lopes-Coelho et al., 2017). New therapeutic targets in the lipid metabolic course have also been pointed out by us in breast cancer, such as fatty acids transporter protein 1, FATP1 (Lopes-Coelho et al, 2018). The genetic background underlying mechanisms of resistance in cancer is a crucial issue in our research and we have disclosed hepatocyte nuclear factor  (HNF1 as the main responsible for the thiold (cysteine and glutathione) dynamic pattern responsible for the resistance to oxidative/alkylant therapy used in cancer treatment (Lopes-Coelho et al., 2016; Nunes et al, 2018).
Currently, we are developing strategies to abrogate the function of FATP1 to destabilize cancer microenvironment metabolic cross-talks, and the cysteine uptake by inhibiting transporters EAAT3 and xCT to overcome cancer resistance.

A more recent and promising project concerning the role of monocytes in cancer neangiogenesis is being developed, assessing the metabolic dynamic along monocytes differentiation.


Projects as PI:

2017-2019-Targeting monocytes as angiogenesis promoters in cancer- New application for old drugs; Funded by iNOVA4Health, FCT

2015-2017- Ovarian cancer (OC) a suitable model to define metabolic profile as a tool to predict chemoresistance; Funded by iNOVA4Health, FCT

2011-2013- "Monocarboxylate transporters (MCTs) as putative therapeutic targets in acute myeloid leukaemia (AML)"- Terry Fox; Liga Portuguesa Contra o Cancro, Núcleo Regional Sul (PI: Jacinta Serpa, CEDOC-FCM-UNL; CIPM-IPOLFG)

2011-2013- "Role of Lactate Rich Microenvironment in Uterine Cervix Cancer Progression"- Fundação Luso-Americana para o Desenvolvimento (FLAD) (PI: Jacinta Serpa, CEDOC-FCM-UNL)

Member of the following projects:

2016-2018- (per)Sulfidomics: benchmarking mechanisms underlying drug toxicity and drug resistance in precision medicine; Funded by iNOVA4Health, FCT

2015-2017-Molecular mechanisms of cell migration and invasion: developing a new strategy to impair tumor progression; Funded by iNOVA4Health, FCT

2014-2016- Projecto supported by LRI Innovative Science Award 2014; PI: Doutora Alexandra Antunes

2014/2016- “Biomarcadores e potenciais alvos terapêuticos em carcinoma do colo uterino”; Terry Fox- Liga Portuguesa Contra o Cancro e Embaixada do Canadá; PI: Ana Félix.

2013/2016- “Risco de Cancro Familiar e Individual – Identificação de Novos Genes” ; Projeto TVI

May 2013- PTDC/BIM-ONC/1242/2012: "Metaboloma do líquido cefalorraquidiano em doentes oncológicos”- PI: Tânia Carvalho- IMM

Selected Publications:

Book chapters:

  • Dynamics of VEGF-A and its Receptors in Cancer Vascularization – an Overview; Domingues, G; Gouveia-Fernandes, S.; Serpa, J.; Capítulo do livro: Recent Cancer Research and Treatment; IConcept Press - ISBN 978-1-922227-386
  • Uterine Cervix Cancer Cells Re-Establish the Natural Lactate Rich Microenvironment, favoring Disease Progression; Jacinta Serpa; Capitulo de Livro; Open access e-Books, Research & Reviews on Cervical Cancer; ISBN 978-81-935757-4-1



  • Lopes-Coelho F, Gouveia-Fernandes S, Serpa J. (2018) Cooperation of cancer and normal cells is pivotal in cancer metabolic fitness. Tumour Biol. 2018 Feb;40(2):1010428318756203. doi: 10.1177/1010428318756203.
  • Lopes-Coelho F, Gouveia-Fernandes S, Nunes SC, Serpa J. (2018) Metabolic Dynamics in Breast Cancer: Cooperation between Cancer and Stromal Cells. Journal of Clinical Breast Cancer Research, accepted
  • Alteriis D, Cartenì F , Parascandola P, Serpa J , Mazzoleni S. (2018) Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death. Cell Cycle accepted
  • Graça G. Desterro J, Sousa J, Fonseca C, Silveira M, Serpa J, Carvalho T, da Silva MG, Gonçalves LG. Identification of putative biomarkers for leptomeningeal invasion in B-cell non-Hodgkin lymphoma by NMR metabolomics. Metabolomics (2017) 13: 136.
  • Grilo NM, João Correia M, Miranda JP, Cipriano M, Serpa J, Matilde Marques M, Monteiro EC, Antunes AMM, Diogo LN, Pereira SA. Unmasking efavirenz neurotoxicity: Time matters to the underlying mechanisms. Eur J Pharm Sci. 2017 May 6;105:47-54. doi: 10.1016/j.ejps.2017.05.010.
  • Lopes-Coelho F, Nunes C, Gouveia-Fernandes S, Rosas R, Silva F, Gameiro p, Carvalho T, Silva MG, Cabeçadas J, Dias, S, Gonçalves LG, Serpa J. Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells. Oncotarget, 2017 Aug 16;8(47):82803-82823 doi: 10.18632/oncotarget.20294.
  • Gouveia-Fernandes S, Carvalho T, Domingues G, Bordeira-Carriço R, Dias S, Serpa J. Colorectal Cancer Aggressiveness is Related to Fibronectin Over Expression, Driving the Activation of SDF-1:CXCR4 Axis. Int J Cancer Clin Res 2016, 3:072:3(8) ISSN: 2378-3419
  • Lopes-Coelho F, André S, Félix A, Serpa J. Breast cancer metabolic cross-talk: Fibroblasts are hubs and breast cancer cells are gatherers of lipids. Mol Cell Endocrinol. 2017 Jan 22. pii: S0303- 7207(17)30044-8. doi:10.1016/j.mce.2017.01.031. 3.
  • Silva F, Félix A, Serpa J. Functional redundancy of the Notch pathway in ovarian cancer cell lines. Oncol Lett. 2016 Oct;12(4):2686-2691. DOI: 10.3892/ol.2016.4959
  • Lopes-Coelho F, Gouveia-Fernandes S, Gonçalves LG, Nunes C, Faustino I, Silva F, Félix A, Pereira SA, Serpa J. HNF1ß drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC).Tumour Biol. 2016 Apr;37(4):4813-29. doi: 10.1007/s13277-015-4290-5.
  • Silva LS, Goncalves LG, Silva F, Domingues G, Maximo V, Ferreira J, Lam EW, Dias S, Felix A, Serpa J. STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment.Tumour Biol. 2016 Apr;37(4):5385-95. doi: 10.1007/s13277-015-4385-z. Epub 2015 Nov 12. doi: 10.1007/s13277-015-4385-z.
  • Serpa, J.; Dias, S. Metabolic cues from the microenvironment act as a major selective factor for cancer progression and metastases formation. Cell Cycle. 2011 Jan 15;10(2):180-1. Epub 2011 Jan 15 DOI: 10.4161/cc.10.2.14476
  • Serpa, J.; Caiado, F.; Carvalho, T.; Torre, C.; Casalou, C.; Gonçalves, L.; Lamosa, P.; Rodrigues, M.; Zhu, Z.; Lam, E.W.-F.; Dias, S. Butyrate rich colonic microenvironment is a relevant selection factor for metabolically adapted tumour cells. J. Biol. Chem. 2010 Dec 10;285(50):39211-23. doi:10.1074/jbc.M110.156026.
  • Cachaço, A.S.; Carvalho, T.; Santos, A.C.; Igreja, C.; Fragoso, R.; Osório, C.; Ferreia, M.; Serpa, J.; Correia, S.; Pinto-do-Ó, P.; Dias S. TNF- Regulates the effecs of irradiation in the mouse bome marrow microenvironment. PLoS One. 2010 Feb 1;5(2):e8980. doi: 10.1371/journal.pone.0008980.
  • Gomes, A.; Carvalho, T.; Serpa, J., Torre, C.; Dias, S. Hypercholesterolemia promotes bone marrow cell mobilization by perturbing the SDF1:CXCR4 axis.Blood. 2010 May 13;115(19):3886-94. Epub 2009 Dec 15. doi: 10.1182/blood-2009-08-240580.
  • Azevedo, M.; Eriksson, S.; Mendes, N.; Serpa, J.; Figueiredo, C.; Resende, L.P.; Ruvoën-Clouet, N.; Haas, R.M; Borén, T.; LePendu, J.; David, L. (2008) Expressing the BabA Adhesin is Influenced by the Secretor Phenotype. Journal of Pathology, 215: 308–16 DOI: 10.1002/path.2363
  • Mesquita, P.; Almeida, R.; Lunet, N.; Reis, C. A.; Santos Silva, L.F.; Serpa, J.; van Seuningen, I.; Barros, B.; David, L. (2006) Metaplasia - A Transdifferentiation process that facilitates cancer development. The model of gastric intestinal metaplasia. Critical ReviewsTM in Oncogenesis 12(1-2):3-26
  • Serpa, J.; Mesquita, P.; Mendes, N.; Oliveira, C.; Almeida, R.; Santos Silva, F.; Reis, C.; Le Pendu, J.; David, L. (2005) Expression of Lea in gastric cancer cell lines depends on FUT3 expression regulated by promoter methylation. Cancer Letters 242(2):191-7 DOI: 10.1016/j.canlet.2005.11.009
  • Serpa, J.; Mendes, N.; Reis, C. A.; Santos Silva, L. F.; Almeida, R.; LePendu, J. and David, L. (2204) Two new FUT2 missense polymorphisms, 739G>A and 839T>C, are partly responsible for non-secretor status in a Caucasian population from Northern Portugal. Biochemical Journal, Nov 1;383(Pt. 3):469-74. DOI: 10.1042/BJ20040803
  • Serpa, J., Lunet, N., Mendes, N., Barros, H. and David, L.(2004) Letter to the Editor: Lewis and Secretor status and Helicobacter pylori eradication. Epidemiol. Infect. 2004 Oct;132(5):997-8
  • Nogueira, A.M.; Marques, T.; Soares, P.C.; David, L.; Reis, C.A.; Serpa, J.; Queiroz, D.M.; Rocha, G.A. and Rocha, A.C. (2003) Lewis antigen expression in gastric mucosa of children: relationship with Helicobacter pylori infection. Journal of Pediatric Gastroenterology and Nutrition vol 38(1): 85-91.
  • Mesquita, P.; Jonckheere, N.; Almeida, R.; Ducourouble, M.P.; Serpa, J.; Silva, E.; Pigny, P.; Santos-Silva, F.; Reis, C.; Silberg, D.; Van Seuningen, I. and David, L. (2003) Human MUC2 mucin gene is transcriptionally regulated by Cdx homeodomain proteins in gastrointestinal carcinoma cell lines. Journal of Biological Chemistry vol 278(51): 51549-56 DOI: 10.1074/jbc.M309019200
  • Serpa, J. , Almeida, R., Oliveira, C., Santos Silva, F., Silva, E., Reis, C., Le Pendu, J., Oliveira, G., Cunha Ribeiro, L. M. and David, L. (2003) Lewis enzyme (alpha 1-3/4 fucosyltransferase) point mutations do not explain the Lewis phenotype in the gastric mucosa of a Portuguese population. Journal of Human Genetics vol 48 pp 183-189. DOI: 10.1007/s10038-003-0007-5
  • Silva, E.; Teixeira, A.; David, L.; Carneiro, F.; Reis, C.; Sobrinho-Simões, J.; Serpa, J.; Veerman, E.; Bolscher, J. e Sobrinho-Simões, M. (2002). Mucins as key molecules for the classification of intestinal metaplasia of the stomach. Virchows Archiv vol 440(3) pp 311-317 DOI: 10.1007/s004280100531
  • Morais, V. A.; Serpa, J.; Palma, A. S.; Costa, T.; Maranga, L. e Costa, J. (2001). Expression and characterisation of recombinant human alpha3/4-Fucosyltransferase III from Sf9 and Tn cells using the baculovirus expression system. Biochemical Journal vol 353 pp 719-725


- Eric WF Lam - Imperial college London, Faculty of Medicine, Department of Surgery & Cancer, UK
- Stefaan van Gool- University of Leuven
- Shinozuka Tsuyoshi - Daiichi Sankyo Co., Ltd
- João Nuno Moreira - Centro de Neuro-ciências da Universidade de Coimbra
- Valdemar Máximo- IPATIMUP e Faculdade de Medicina da Universidade do Porto
- José Cabeçadas - Instituto Português de Oncologia de Lisboa, Francisco Gentil
- Maria Gomes da Silva - Instituto Português de Oncologia de Lisboa, Francisco Gentil
- Ana Félix- Instituto Português de Oncologia de Lisboa, Francisco Gentil
- António Almeida - Instituto Português de Oncologia de Lisboa, Francisco Gentil e Hospital da Luz
- Saudade André - Instituto Português de Oncologia de Lisboa, Francisco Gentil
- Margarida Silveira - Instituto Português de Oncologia de Lisboa, Francisco Gentil
- Duarte Salgado - Instituto Português de Oncologia de Lisboa, Francisco Gentil
- Vasco Bonifácio - Instituto Superior Técnico da Universidade de Lisboa
- Alexandra Antunes - Instituto Superior Técnico da Universidade de Lisboa
- João B Vicente - Instituto de Tecnologia Química e Biológica
- Luís G Gonçalves - Instituto de Tecnologia Química e Biológica
- Sofia A Pereira – CEDOC, NOVA Medical School
- Duarte Barral – CEDOC, NOVA Medical School
- Cristina Casalou – CEDOC, NOVA Medical School

Team photos

No open positions.