Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells

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 tand...

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Bibliographic Details
Published in:Molecular biology of the cell 2015-11, Vol.26 (22), p.4163-4170
Main Authors: Cooper, Sam, Sadok, Amine, Bousgouni, Vicky, Bakal, Chris
Format: Article
Language:English
Subjects:
Animals
Cattle
Cell Line, Tumor
Cell Movement - physiology
Cell Shape - physiology
Collagen - metabolism
Humans
Melanoma - pathology
Mesoderm - metabolism
Neoplasm Invasiveness
Polar Bodies - metabolism
rho GTP-Binding Proteins - metabolism
Signal Transduction
Structure-Activity Relationship
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E15-06-0382