title: Directed migration of cancer cells guided by the graded texture of the underlying matrix.
abstract: Living cells and the extracellular matrix (ECM) can exhibit complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration-which we term 'topotaxis'-guided by the gradient of the nanoscale topographic features in the cells' ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI(3)K-Akt and ROCK-MLCK. In melanoma cancer cells, this balance can be altered by different ECM inputs, pharmacological perturbations or genetic alterations, particularly a loss of PTEN in aggressive melanoma cells. We conclude that topotaxis is a product of the material properties of cells and the surrounding ECM, and propose that the invasive capacity of many cancers may depend broadly on topotactic responses, providing a potentially attractive mechanism for controlling invasive and metastatic behaviour.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06520, USA.|Yale Systems Biology Institute, Yale University, West Haven, Connecticut 06516, USA.|Departments of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: JinSeok
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hong-Nam
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Departments of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Chiaochun Joanne
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Moon Kyu
authors.initials: MK
authors.lastname: Kwak
authors.affiliation: Departments of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Eunmi
authors.initials: E
authors.lastname: Hur
authors.affiliation: Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Kahp-Yang
authors.initials: KY
authors.lastname: Suh
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: An
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06520, USA.|Yale Systems Biology Institute, Yale University, West Haven, Connecticut 06516, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008545:Melanoma / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013499:Surface Properties; D000071442:Taxis Response / Q000502:physiology*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D054460:rho-Associated Kinases; D051059:PTEN Phosphohydrolase