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 tha...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?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 restoredβ8 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.展开更多
Dear Editor,Genetic variant Delta(B.1.617.2)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which possesses a remarkable ability to transmit and spread,is currently becoming predominant worldwide.Despit...Dear Editor,Genetic variant Delta(B.1.617.2)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which possesses a remarkable ability to transmit and spread,is currently becoming predominant worldwide.Despite its great harm to human beings,how the Delta variant with T478K,P681R and L452R mutations achieves its ultrafast spread remains elusive.Entry of SARS-CoV-2 into host cells is mediated by a rapid enzymatic hydrolysis.展开更多
Dear Editor,Alveolar macrophages(AMs)are among the first immune cells to encounter SARS-CoV-2 during an infection due to their abundant numbers and physical location in the lungs.Thus,the reaction of AMs to SARS-CoV-2...Dear Editor,Alveolar macrophages(AMs)are among the first immune cells to encounter SARS-CoV-2 during an infection due to their abundant numbers and physical location in the lungs.Thus,the reaction of AMs to SARS-CoV-2 has a profound impact on the outcome of the infection.In most cases,AMs can release cytokines and prime adaptive T-and B-cell immune responses to resolve the infection.展开更多
基金supported by National Natural Science Foundation of China grant nos.82388201 to B.H.and 82003145 to J.L.Haihe Laboratory of Cell Ecosystem Innovation Fund grant no.22HHXBSS00009 to B.H.+1 种基金National Key Research and Development Program of China grant no.2022YFA1206000CAMS Innovation Fund for Medical Sciences(CIFMS)grant nos.2021-I2M-1-021 and 2022-I2M-JB-008 to B.H.
文摘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?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 restoredβ8 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.
基金This work was supported by the National Natural Science Foundation of China(81788101,82041008)Chinese Academy of Medical Sciences(CAMS)Initiative for Innovative Medicine(2021-I2M-1-021).
文摘Dear Editor,Genetic variant Delta(B.1.617.2)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which possesses a remarkable ability to transmit and spread,is currently becoming predominant worldwide.Despite its great harm to human beings,how the Delta variant with T478K,P681R and L452R mutations achieves its ultrafast spread remains elusive.Entry of SARS-CoV-2 into host cells is mediated by a rapid enzymatic hydrolysis.
基金This work was supported by the National Natural Science Foundation of China(81788101)CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-021).
文摘Dear Editor,Alveolar macrophages(AMs)are among the first immune cells to encounter SARS-CoV-2 during an infection due to their abundant numbers and physical location in the lungs.Thus,the reaction of AMs to SARS-CoV-2 has a profound impact on the outcome of the infection.In most cases,AMs can release cytokines and prime adaptive T-and B-cell immune responses to resolve the infection.
