title: Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells.
abstract: Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space--an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively.
authors: Division of Cancer Cell Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom Department of Computational Systems Medicine, Imperial College, London, South Kensington Campus, London SW7, United Kingdom sc2011@ic.ac.uk chris.bakal@icr.ac.uk.
authors: Sam
authors: S
authors: Cooper
authors: Division of Cancer Cell Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom.
authors: Amine
authors: A
authors: Sadok
authors: Division of Cancer Cell Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom.
authors: Vicky
authors: V
authors: Bousgouni
authors: Division of Cancer Cell Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom sc2011@ic.ac.uk chris.bakal@icr.ac.uk.
authors: Chris
authors: C
authors: Bakal
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D048430:Cell Shape / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D008648:Mesoderm / Q000378:metabolism; D009361:Neoplasm Invasiveness; D059705:Polar Bodies / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D003094:Collagen; D020741:rho GTP-Binding Proteins