RG14: Cell Metabolism and Cancer
RG14 is interested in understanding how cellular metabolism regulates tissue repair and cell fate decisions, and how metabolism misregulation can lead to uncontrolled proliferation and tumour formation. Although the characteristic profile of tumours has been known for several decades it is still not clear what is the functional role of metabolism in tumours.
The group is constituted by three teams working on molecular mechanisms using animal models (C Homem, A Jacinto, and A Gontijo) and integrates two senior oncologists (D Arnold and S Braga) who contribute for the development and supervision of translational cancer research projects.
Drosophila brain tumours are used as a model to understand how metabolism contributes for tumour cell transformation and tumour growth. The group has shown that proliferation of Drosophila neural stem cells is dependent on glycolysis, and that an increase in Oxidative Phosphorylation leads to stem cell differentiation and therefore cell-cycle exit. Additionally, it has been shown that Drosophila brain tumours are highly dependent on glycolysis. This is consistent with what has been described for human tumours, which are highly dependent on glycolysis even in the presence of oxygen, the so-called Warburg effect.
The group is also interested in understanding the molecular and cellular mechanisms that drive regeneration and repair of tissues and organs and how misregulation of such mechanisms is involved in cancer. They have shown that cell metabolism reprograming plays a key role in tissue regeneration using Drosophila and zebrafish, and are now exploring the signaling pathways that regulate reprograming in this context.
Finally, the group is working on neuroendocrine control of development in Drosophila, studying how tumours growing in peripheral tissues communicate - via hormones - with the central nervous system.
Keywords: Cell fate; Glycolysis; Regeneration; Reprograming
Carvalho C, Patricio P, Ponte S, Heisenberg CP, Almeida L, Nunes AS, Araújo NAM, Jacinto A (2018) Occluding junctions as novel regulators of tissue mechanics during wound repair. Journal of Cell Biology 217(12): 4267
Marques J, Teixeira V, Jacinto A, Tavares A (2018) Identification of Novel Hemangioblast Genes in the Early Chick Embryo. Cells 7(2):9
Cristo I, Carvalho L, Ponte S, Jacinto A (2018) Novel role for Grainy head in the regulation of cytoskeletal and junctional dynamics during epithelial repair. Journal of Cell Science 131: jcs.213595
Coelho S, Cabral G, Lopes JA, Jacinto A (2018) Renal regeneration after acute kidney injury. Nephrology 23(9):805–814
Gontijo A, Garelli A (2018) The biology and evolution of the Dilp8-Lgr3 pathway: a relaxin-like pathway coupling tissue growth and developmental timing control. Mechanisms of development 154:44-50