Metastasis is the primary cause of cancer related deaths. Crucially, any potential treatment of metastasis, which may target increased migration, needs to take into account that cancer cell migration is plastic, i.e. that cancer cells can easily switch between a mesenchymal and a contractility driven amoeboid migration mode. The latter mode can be induced by confining cells. However, it is not known how cancer cells can actively switch between these two modes. In this project, you will explore a novel mechanosensor that may act as a physiological switch between mesenchymal and amoeboid 3D cancer cell migration.
1.Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, Sahai E, Marshall CJ.
Rac activation and inactivation control plasticity of tumor cell movement.
Cell. 2008 Oct 31;135(3):510-23. doi: 10.1016/j.cell.2008.09.043.
2. Krause M, Gautreau A.
Steering cell migration: lamellipodium dynamics and the regulation of directional persistence.
Nat Rev Mol Cell Biol. 2014 Sep;15(9):577-90. doi: 10.1038/nrm3861
3.Carmona G, Perera U, Gillett C, Naba A, Law AL, Sharma VP, Wang J, Wyckoff J, Balsamo M, Mosis F, De Piano M, Monypenny J, Woodman N, McConnell RE, Mouneimne G, Van Hemelrijck M, Cao Y, Condeelis J, Hynes RO, Gertler FB, Krause M.
Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE.
Oncogene. 2016 Sep 29;35(39):5155-69. doi: 10.1038/onc.2016.47. Epub 2016 Mar 21.
4. Charras G, Sahai E.
Physical influences of the extracellular environment on cell migration.
Nat Rev Mol Cell Biol. 2014 Dec;15(12):813-24. doi: 10.1038/nrm3897. Epub 2014 Oct 30
5.Georgouli M, Herraiz C, Crosas-Molist E, Fanshawe B, Maiques O, Perdrix A, Pandya P, Rodriguez-Hernandez I, Ilieva KM, Cantelli G, Karagiannis P, Mele S, Lam H, Josephs DH, Matias-Guiu X, Marti RM, Nestle FO, Orgaz JL, Malanchi I, Fruhwirth GO, Karagiannis SN, Sanz-Moreno V.
Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment.
Cell. 2019 Feb 7;176(4):757-774.e23. doi: 10.1016/j.cell.2018.12.038. Epub 2019 Jan 31.