Plasticity of cancer cell invasion: Patterns and mechanisms

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Top Highlights

• 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