Where Ideas grow

Cytoskeletal Regulation & Cancer

ABOUT

The main interest of our team is to understand how actin deregulation underlies benign tumour development and their progression into invasive cancer using the in vivo model Drosophila melanogaster; inducible human cell lines that recapitulate the multistep development of cancer; tumour samples and computational modelling.

 

RESEARCH

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.

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.

Selected Publications

Janody F.,
The Big Bang of tissue growth: Apical cell constriction turns into tissue expansion. Journal of Cell Biology217(3):807-808, 2018. [Journal: Note] [IF: 8,9]
DOI: 10.1083/jcb.201801076 SCOPUS: 85042848294. .

Tavares S., Vieira A.F., Taubenberger A.V., Araújo M., Martins N.P., Brás-Pereira C., Polónia A., Herbig M., Barreto C., Otto O., Cardoso J., Pereira-Leal J.B., Guck J., Paredes J., Janody F.,
Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells. Nature Communications8:, 2017. [Journal: Article] [CI: 27] [IF: 12,4]
DOI: 10.1038/ncomms15237 SCOPUS: 85019618841. .

Brás-Pereira C., Potier D., Jacobs J., Aerts S., Casares F., Janody F.,
dachshund Potentiates Hedgehog Signaling during Drosophila Retinogenesis. PLoS Genetics12(7):, 2016. [Journal: Article] [CI: 7] [IF: 6,1]
DOI: 10.1371/journal.pgen.1006204 SCOPUS: 84982854129. .

Gaspar P., Holder M.V., Aerne B.L., Janody F., Tapon N.,
Zyxin antagonizes the FERM protein expanded to couple f-actin and yorkie-dependent organ growth. Current Biology25(6):679-689, 2015. [Journal: Article] [CI: 33] [IF: 9]
DOI: 10.1016/j.cub.2015.01.010 SCOPUS: 84926322744. .

Brás-Pereira C., Casares F., Janody F.,
The retinal determination gene dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex. Development142(8):1470-1479, 2015. [Journal: Article] [CI: 13] [IF: 6,1]
DOI: 10.1242/dev.113340 SCOPUS: 84926380808. .

Caldeira J., Figueiredo J., Brás-Pereira C., Carneiro P., Moreira A.M., Pinto M.T., Relvas J.B., Carneiro F., Barbosa M., Casares F., Janody F., Seruca R.,
E-cadherin-defective gastric cancer cells depend on Laminin to survive and invade. Human Molecular Genetics24(20):5891-5900, 2015. [Journal: Article] [CI: 12] [IF: 6]
DOI: 10.1093/hmg/ddv312 SCOPUS: 84943762566. .

Fernández B.G., Jezowska B., Janody F.,
Drosophila actin-Capping Protein limits JNK activation by the src proto-oncogene. Oncogene33(16):2027-2039, 2014. [Journal: Article] [CI: 24] [IF: 8,5]
DOI: 10.1038/onc.2013.155 SCOPUS: 84899417132. .

Amândio A.R., Gaspar P., Whited J.L., Janody F.,
Subunits of the Drosophila actin-capping protein heterodimer regulate each other at multiple levels. PLoS ONE9(5):, 2014. [Journal: Article] [CI: 6] [IF: 3,2]
DOI: 10.1371/journal.pone.0096326 SCOPUS: 84900398117. .

Fernández B.G., Gaspar P., Brás-Pereira C., Jezowska B., Rebelo S.R., Janody F.,
Actin-capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. Development138(11):2337-2346, 2011. [Journal: Article] [CI: 188] [IF: 6,6]
DOI: 10.1242/dev.063545 SCOPUS: 79956327002. .

Jezowska B., Fernández B.G., Amândio A.R., Duarte P., Mendes C., Brás-Pereira C., Janody F.,
A dual function of Drosophila capping protein on DE-cadherin maintains epithelial integrity and prevents JNK-mediated apoptosis. Developmental Biology360(1):143-159, 2011. [Journal: Article] [CI: 8] [IF: 4,1]
DOI: 10.1016/j.ydbio.2011.09.016 SCOPUS: 80755133315. .