首页|YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

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Solid tumor cells live in a highly dynamic mechanical microenvironment.How the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an enigma.Here,we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like cells.Mechanistically,integrin β8 was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein(YAP).YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G(MAFG),allowing MAFG to transactivate the stemness genes NANOG,SOX2,and NESTIN.Inactivation also restored β8 expression,thereby forming a closed mechanical loop.Importantly,MAFG expression is correlated with worse prognosis.Our findings provide mechanical insights into the regulation of tumor cell dedifferentiation,which has therapeutic implications for exploring innovative strategies to attack malignancies.

Jiadi Lv、Xiao han Liu、Yabo Zhou、Feiran Cheng、Haoran Chen、Shunshun Li、Dianheng Wang、Li Zhou、Zhenfeng Wang、Nannan Zhou、Jie Chen、Bo Huang

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Department of Immunology & State Key Laboratory of Common Mechanism Research for Major Diseases,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College(PUMC),Beijing,100005,China

Department of Histology and Embryology,Basic Medical College,China Medical University,Shenyang,Liaoning 110122,China

Department of Immunology,Basic Medical College,China Medical University,Shenyang,Liaoning 110122,China

Department of Biochemistry & Molecular Biology,Tongji Medical College,Huazhong University of Science & Technology,Wuhan 430030,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaHaihe Laboratory of Cell Ecosystem Innovation FundNational Key Research and Development Program of ChinaNational Key Research and Development Program of China

823882018200314522HHXBSS000092021-I2M-1-0212022-I2M-JB-008

2024

10.34133/research.0215

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(2)
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