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Emerging paradigms in cancer cell plasticity

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초록

Cancer cells metastasize to distant organs by altering their characteristicswithin the tumor microenvironment (TME) to effectivelyovercome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift betweendifferent morphological states to invade, disseminate, and seedmetastasis. The epithelial-to-mesenchymal transition (EMT) is atheory derived from tissue biopsy, which explains the acquisitionof EMT transcription factors (TFs) that convey mesenchymalfeatures during cancer migration and invasion. On theother hand, adherent-to-suspension transition (AST) is an emergingtheory derived from liquid biopsy, which describes theacquisition of hematopoietic features by AST-TFs that reprogramsanchorage dependency during the dissemination of circulatingtumor cells (CTCs). The induction and plasticity of EMT and ASTdynamically reprogram cell-cell interaction and cell-matrix interactionduring cancer dissemination and colonization. Here,we review the mechanisms governing cellular plasticity of ASTand EMT during the metastatic cascade and discuss therapeuticchallenges posed by these two morphological adaptations toprovide insights for establishing new therapeutic interventions.

Abstract

Cancer cells metastasize to distant organs by altering their characteristicswithin the tumor microenvironment (TME) to effectivelyovercome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift betweendifferent morphological states to invade, disseminate, and seedmetastasis. The epithelial-to-mesenchymal transition (EMT) is atheory derived from tissue biopsy, which explains the acquisitionof EMT transcription factors (TFs) that convey mesenchymalfeatures during cancer migration and invasion. On theother hand, adherent-to-suspension transition (AST) is an emergingtheory derived from liquid biopsy, which describes theacquisition of hematopoietic features by AST-TFs that reprogramsanchorage dependency during the dissemination of circulatingtumor cells (CTCs). The induction and plasticity of EMT and ASTdynamically reprogram cell-cell interaction and cell-matrix interactionduring cancer dissemination and colonization. Here,we review the mechanisms governing cellular plasticity of ASTand EMT during the metastatic cascade and discuss therapeuticchallenges posed by these two morphological adaptations toprovide insights for establishing new therapeutic interventions.

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