Cytoskeletal Regulation & Cancer
The main interest of our team is to understand how cytoskeleton-adhesions scaffolds at cell-cell and cell-extracellular matrix contact sites, orchestrate signalling networks to generate distinct cancer phenotypes using the in vivo model Drosophila melanogaster; inducible human cell lines that recapitulate the multistep development of cancer; tumour samples and computational modelling.
Our group has reported molecular mechanisms by which the cytoskeleton regulate cancer signalling activity (2011-Dev.; 2011-Dev. Biol.; 2014-Oncogene; 2014-PLoS One; 2015-Curr. Biol.; 2017-Nat. Comm.; 2019- Sci. Rep.) and issued a spotlight on actin and tissue growth (2018-JCB). We have also revealed a role of the co-repressors Dachshund in coordinating signalling outputs (2015-Dev.; 2016-PLoS Genet.), assessed the role of microenvironmental signals in controlling hybrid EMT phenotypes (2020-Cancer Res.) and their ability to cooperate (2021-IJMS). Taken together, our work has contributed to unveil molecular mechanisms by which the actin cytoskeleton conveys signals at adhesion sites to intracellular signalling pathways, leading to activation of cancer transcriptional programs.
Building up on our findings, we are currently working on the premise that cytoskeleton-adhesions scaffolds at cell-cell and cell-extracellular matrix contact sites orchestrate signalling networks to generate distinct cancer phenotypes. We are actively engaged in singling out the composition of the cytoskeleton-adhesions scaffolds involved and of signalling networks they control. We are also searching for signals from the tumour microenvironment, which affect the response of cytoskeleton-adhesions scaffolds in the context of carcinogenesis.
Our work should permit addressing fundamental questions in cell biology, such as how the coordinated interplay between cytoskeleton-adhesion scaffolds leads to the spatial organization of molecular signals and forces and on how it shapes the way cells communicate with their environment. Importantly, the knowledge arising from our work may ultimately translate into tools that are relevant for the therapeutic intervention of cancer.
Hybrid epithelialmesenchymal phenotypes are controlled by microenvironmental factors. Cancer Research80(11):2407-2420, 2020. [Journal: Article] [CI: 2] [IF: 9,7 (*)]
DOI: 10.1158/0008-5472.CAN-19-3147 SCOPUS: 85085904168. .
Jain P.B., Guerreiro P.S., Canato S., Janody F.,
The spectraplakin Dystonin antagonizes YAP activity and suppresses tumourigenesis. Scientific Reports9(1):, 2019. [Journal: Article] [CI: 1] [IF: 4]
DOI: 10.1038/s41598-019-56296-z SCOPUS: 85077305562. .
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: 51] [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: 8] [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: 38] [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: 13] [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: 9] [IF: 3,2]
DOI: 10.1371/journal.pone.0096326 SCOPUS: 84900398117. .