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- W4319880297 abstract "Tumor cells are generally softer than healthy cells and tumor cells with high self-renewal or malignancy exhibit even lower stiffness, suggesting the inverse correlation between cellular stiffness and malignant potential. However, it remains mysterious whether tumor cell softening is a by-product of or a driving force for tumor progression. In this study, hepatocellular carcinoma (HCC) was chosen as a model of disease. The stiffness of various HCC cells was modulated by targeting actomyosin activity through both genetic and pharmaceutical approaches. Softening and stiffening tumor cells promotes and suppresses their self-renewal in vitro and tumor formation/growth in vivo, suggesting the regulatory role of cell mechanics in self-renewal and tumorigenicity. These findings are also observed in multiple other cancer types, including breast, lung, colon, and cervical cancer. Mechanistically, softening/stiffening cytoskeleton weakens/strengthens the interaction between APC and β-catenin, which inhibits/enhances β-catenin degradation and promotes/suppresses its nuclear translocation. Nuclear β-catenin binds the promoter of the stemness gene Oct4 and facilitates its transcription, which enhances tumor cell self-renewal. Further, cell softening facilitates the de-differentiation of non-CSCs into cancer stem cells (CSCs), while cell stiffening promotes the differentiation of CSCs into non-CSCs, both of which depend on Wnt/β-catenin signaling. The cytoskeleton-APC-Wnt/β-catenin-Oct4 signaling are correlated in clinical samples and associated with tumor differentiation and patient survival. In summary, our findings demonstrate that actomyosin-mediated mechanical properties of tumor cells dictate their self-renewal and tumorigenicity through cytoskeleton-APC-Wnt/β-catenin-Oct4 signaling, which may identify cell mechanics not only as a marker for diagnosis but also as a new mechanical target for cancer therapeutics." @default.
- W4319880297 created "2023-02-11" @default.
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- W4319880297 date "2023-02-01" @default.
- W4319880297 modified "2023-09-30" @default.
- W4319880297 title "The mechanics of tumor cells dictate malignancy" @default.
- W4319880297 doi "https://doi.org/10.1016/j.bpj.2022.11.2819" @default.
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