Cytoskeleton Regulation and Cancer


The main interest of our team is tounderstand how actin deregulation underlies benign tumour development and their progression into invasive cancerusing the in vivomodel Drosophilamelanogaster; inducible human cell lines that recapitulate the multistep development of cancer; tumour samples and computational modelling.



Our team has demonstrated the existence of reciprocal feedbacks between the actin cytoskeleton and the activity of various oncogenic pathways, including the non-receptor tyrosine kinase Src, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK) and the downstream mediator of the Hippo pathway, Yorkie/YAP/TAZ in the control of proliferative and surviving abilities (Fernandez et al., 2011; Brás-Pereira et al., 2011; Jezowska et al., 2011; Fernandez et al., 2014; Amândio et al., 2014; Gaspar et al., 2015; Tavares et al., 2017). We have also identified the nuclear protein related to the Sno/Ski family of co-repressors Dachshund, as a key regulator of the Hippo and Hedgehog signalling pathways (Bras-Pereira et al., 2015; Bras-Pereira et al., 2016). Taken together, our work permitted to identify novel molecular mechanisms underlying benign disease development and progression, as well as the signals involved in the transmission into invasive disease. We are currently teaming with the Epithelial Interactions in Cancer group at i3S to identify molecular principles governing Cancer Stem-like Cell Biology in the frame of the CANCEL STEM Consortium.


Selected Publications

  • Tavares S., Vieira A., Taubenberg A.V., Araujo M.; Martins N.P.; Brás-Pereira C; Polónia A., Herbig M., Barreto C., Otto O. Cardoso J., Pereira Leal J., GuckJ., Paredes J. and Janody F.(2017). Actin stress fiber organization promotes cell stiffening and proliferation of pre-malignant breast tumors. Nat Comm.May 16; 8:15237.
    DOI: 10.1038/ncomms15237.
  • Brás-Pereira C, Potier D, Jacobs J, Aerts S, Casares F, Janody F.(2016). dachshundpotentiates Hedgehog signaling during Drosophilaretinogenesis. PLoS Genet. Jul 21;12(7):e1006204.
    DOI: 10.1371/journal.pgen.1006204.
  • Caldeira J.,Figueiredo J., Brás-Pereira C., Pinto M. T., Relvas J.B., Barbosa M., Casares F., Janody F., Seruca R. (2015). E-cadherin-defective Gastric Cancer Cells Depend on Laminin to Survive and Invade. Hum Mol Genet. Vol 24 Issue 20:5891-5900.
    DOI: 10.1093/hmg/ddv312.
  • Brás-Pereira C., Casares F. and Janody F.(2015). The retinal determination gene dachshundrestricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex. Development Apr 15;142(8):1470-9.
    DOI: 10.1242/dev.113340.
  • Gaspar P., Holder M., Russell M., Collinson L., Janody F.and Tapon N. (2015). Zyxin antagonizes the FERM protein Expanded to couple F-actin and Yorkie-dependent organ growth. Curr Biol.Mar 16;25(6):679-89.
    DOI: 10.1016/j.cub.2015.01.010.
  • Amândio A. R.; Gaspar P.; Whited J. L. and Janody F. (2014). Subunits of the Drosophilaactin-Capping Protein heterodimer regulate each other at multiple levels. PLoS OneMay 2;9(5).
    DOI: 10.1371/journal.pone.0096326.
  • García Fernández B.,Jezowska B and Janody F. (2014)Drosophila actin Capping Protein limits JNK activation by the Src proto-oncogene. OncogeneApr 17;33(16):2027-39.
    DOI: 10.1038/onc.2013.155.
  • Brás-Pereira C., Zhang T., Pignoni F. and Janody F.(2011). Homeostasis of the Drosophilaadult retina by Capping Protein and the Hippo pathway. Commun.Integr Biol.Sep/Oct.: 612-615.
    DOI: 10.4161/cib.4.5.16853.
  • Jezowska B; García FernándezB.; Amândio A.R.; Duarte P.; Mendes C; Brás-Pereira C. and Janody F. (2011). A dual function of DrosophilaCapping Protein on DE-Cadherin maintains epithelium integrity and prevents JNK-mediated apoptosis. Dev Biol(360), 143-159.
    DOI: 10.1016/j.ydbio.2011.09.016.
  • García FernándezB.; Gaspar P.; Brás-Pereira C.; Jezowska B.; Rebelo S.R.; and Janody F. (2011). Actin-Capping Protein and the Hippo pathway regulate actin accumulation and tissue growth in Drosophila. Development138, 2337-2346.
    DOI: 10.1242/dev.063545.



In situ proximity ligation assay for E-cadherin and p120ctn (red) in MCF10A-ER-Src cells stained with Phalloidin to mark actin filaments (green) and DAPI (blue), which stain the nucleus.



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