Plasticity of Cancer Cell Invasion-Mechanisms and Implications for Therapy.
Cancer cell migration is a plastic and adaptive process integrating cytoskeletal dynamics, cell-extracellular matrix and cell-cell adhesion, as well as tissue remodeling. In response to molecular and physical microenvironmental cues during metastatic dissemination, cancer cells exploit a versatile repertoire of invasion and dissemination strategies, including collective and single-cell migration programs. This diversity generates molecular and physical heterogeneity of migration mechanisms and metastatic routes, and provides a basis for adaptation in response to microenvironmental and therapeutic challenge. We here summarize how cytoskeletal dynamics, protease systems, cell-matrix and cell-cell adhesion pathways control cancer cell invasion programs, and how reciprocal interaction of tumor cells with the microenvironment contributes to plasticity of invasion and dissemination strategies. We discuss the potential and future implications of predicted "antimigration" therapies that target cytoskeletal dynamics, adhesion, and protease systems to interfere with metastatic dissemination, and the options for integrating antimigration therapy into the spectrum of targeted molecular therapies.
David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
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Te Boekhorst
David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Radboud University Medical Centre, Nijmegen, The Netherlands; Cancer Genomics Center (CGC.nl), Utrecht, The Netherlands. Electronic address: pfriedl@mdanderson.org.
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Friedl
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002465:Cell Movement; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D000970:Antineoplastic Agents
Amoeboid movement; Anticancer therapy; Cell adhesion; Collective migration; Epithelial-to-mesenchymal transition; Mesenchymal migration; Metastasis; Plasticity; Proteolysis; Tumor cell invasion