Cancer cells can disseminate and migrate via several alternative mechanisms including amoeboid cell migration, mesenchymal cell migration, and collective cell migration
During tumor progression, cells pass through complex microenvironments and adapt their migration strategies by reversible mesenchymal-amoeboid and individual-collective transitions
This plasticity in motility patterns enables cancer cells disseminate further and thus limit the efficiency of anti-metastasis therapies.
Mesenchymal cells, exhibiting elongated morphology, can move forward by generating traction force via cytoskeletal contractility and integrin-mediated ECM-adhesion
Proteolysis-dependent ECM degradation is also required for mesenchymal tumor cells to generate paths for their migration
Conversely, amoeboid cells with rounded and deformable morphology can squeeze through narrow spaces and smaller pores of the ECM in the absence of proteolysis-dependent ECM remodeling
During this type of movement, the cells exhibit bleb-like protrusions driven by actomyosin contractility and maintain weak and dynamic cell adhesion to ECM, resulting in high-speed movement
collective cell migration is a movement pattern of multiple cells that retain cell-cell connections and migrate coordinately
This type of tumor cell movement depends on actin dynamics, integrin-based ECM adhesion, and proteolytic cleavage of ECM.
migrating cohesive groups comprise heterogeneous tumor cells
Clinically, collective and single-cell patterns are often detected within the same tumor microenvironment by histological examination
plasticity of tumor migration modes
Depending on tissue context or the mechanical and biochemical cues from the ECM, tumor cells may switch their migration modes including reversible collective-individual and mesenchymal-amoeboid transitions
This type of migration is characterized by loss of intercellular connections and dissemination as a single tumor cell.
When tumor cells squeeze through pores smaller than their cell diameter, the nucleus can be deformed into a maximum compressed state
bleb-like protrusions of the cell membrane
These protrusions enable cells to sense the microenvironment by mechanotransduction and allow penetration through narrow spaces
The bleb-like protrusions and cortical actin cytoskeleton dynamics are predominately regulated by the small GTPase RhoA as well as its effector, Rho-associated kinase (ROCK)
amoeboid migration of tumor cells can occur without proteolytical ECM reorganization
lack of strong cell-ECM interactions
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