-
摘要: 单个或群体细胞的生物活动有多种信号通信方式,已被阐明的方式包括神经元电信号通信、激素介导的长距离通信以及细胞分泌到胞外的短程信号通信等。近来大量研究表明机械应力也参与了细胞间或细胞与外界的信息交互,尤其是上皮细胞间或上皮细胞与细胞外基质间的信号通信。由机械应力引发的细胞通信瞬时快速,且影响单个上皮细胞和上皮细胞集群的各种活动。机械应力引发的细胞通信作用介质包括肌动蛋白、肌球蛋白、细胞骨架和黏附连接等,这些介质通过机械信号触发离子流动、信号通路激活和转录因子调控等进程,由此干预细胞行为。该文从生物信号、三维折叠、集体迁移、细胞代谢、癌变和上皮-间质转化等多个方面阐述机械应力对上皮细胞的影响。Abstract: There are multiple signaling communication modalities for the biological activities of single cells or groups of cells. The elucidated modalities include neuronal electrical signal communication, long-distance communication mediated by hormones, and short-range signal communication secreted by cells into the extracellular environment, etc. Recently, many studies have shown that mechanical forces are also extensively involved in the information exchange between cells or between cells and the external environment, especially in the signal communication among epithelial cells or between epithelial cells and the extracellular matrix. The cell communication triggered by mechanical forces is instantaneous and rapid, and it affects various activities of both individual epithelial cells and epithelial cell clusters. The mediators of cell communication induced by mechanical forces include actin, myosin, cytoskeleton, and adherens junctions, etc. These mediators trigger processes such as ion flow, activation of signaling pathways, and regulation of transcription factors through mechanical signals, thereby interfering with cell behaviors. This article elaborates on the impacts of mechanical forces on epithelial cells from multiple aspects, including biological signals, three-dimensional folding, collective migration, cell metabolism, carcinogenesis, and epithelial-mesenchymal transition.
-
参考文献
(48) [1] De BellyH,YanS,Borja da RochaH,et al.Cell protrusions and contractions generate long-range membrane tension propagation[J].Cell,2023,186(14):3049-3061.e15.DOI: 10.1016/j.cell.2023.05.014. [2] XiaoR, LiuJ, XuXZS. Mechanosensitive GPCRs and ion channels in shear stress sensing[J]. Curr Opin Cell Biol, 2023, 84: 102216.DOI: 10.1016/j.ceb.2023.102216. [3] WangS,LiW,ZhangP,et al.Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx[J].J Adv Res,2022,41:63-75.DOI: 10.1016/j.jare.2022.01.004. [4] Servin-VencesMR,LamRM,KoolenA,et al.PIEZO2 in somatosensory neurons controls gastrointestinal transit[J].Cell,2023,186(16):3386-3399.e15.DOI: 10.1016/j.cell.2023.07.006. [5] SwainSM,LiddleRA.Mechanosensing Piezo channels in gastrointestinal disorders[J].J Clin Invest,2023,133(19):e171955.DOI: 10.1172/JCI171955. [6] JeongH,ClarkS,GoehringA,et al.Structures of the TMC-1 complex illuminate mechanosensory transduction[J].Nature,2022,610(7933):796-803.DOI: 10.1038/s41586-022-05314-8. [7] YueX,ShengY,KangL,et al.Distinct functions of TMC channels: a comparative overview[J].Cell Mol Life Sci,2019,76(21):4221-4232.DOI: 10.1007/s00018-019-03214-1. [8] JinP,BulkleyD,GuoY,et al.Electron cryo-microscopy structure of the mechanotransduction channel NOMPC[J].Nature,2017,547(7661):118-122.DOI: 10.1038/nature22981. [9] RoyChoudhury A,GroßhansJ,KongD.Ion channels in epithelial dynamics and morphogenesis[J].Cells,2021,10(9):2280.DOI:1 0.3390/cells10092280. [10] DriskillJH,PanD.Control of stem cell renewal and fate by YAP and TAZ[J].Nat Rev Mol Cell Biol,2023,24(12):895-911.DOI: 10.1038/s41580-023-00644-5. [11] WangY,ShiR,ZhaiR,et al.Matrix stiffness regulates macrophage polarization in atherosclerosis[J].Pharmacol Res,2022,179:106236.DOI: 10.1016/j.phrs.2022.106236. [12] FargeE.Mechanical induction of Twist in the Drosophila foregut/stomodeal primordium[J].Curr Biol,2003,13(16):1365-1377.DOI: 10.1016/s0960-9822(03)00576-1. [13] Fernández-SánchezME,BarbierS,WhiteheadJ,et al.Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure[J].Nature,2015,523(7558):92-95.DOI: 10.1038/nature14329. [14] WangYC.The origin and the mechanism of mechanical polarity during epithelial folding[J].Semin Cell Dev Biol,2021,120:94-107.DOI: 10.1016/j.semcdb.2021.05.027. [15] HeerNC,MillerPW,ChanetS,et al.Actomyosin-based tissue folding requires a multicellular myosin gradient[J].Development,2017,144(10):1876-1886.DOI: 10.1242/dev.146761. [16] FierlingJ,JohnA,DelormeB,et al.Embryo-scale epithelial buckling forms a propagating furrow that initiates gastrulation[J].Nat Commun,2022,13(1):3348.DOI: 10.1038/s41467-022-30493-3. [17] MonierB,GettingsM,GayG,et al.Apico-basal forces exerted by apoptotic cells drive epithelium folding[J].Nature,2015,518(7538):245-248.DOI: 10.1038/nature14152. [18] BlonskiS,AureilleJ,BadawiS,et al.Direction of epithelial folding defines impact of mechanical forces on epithelial state[J].Dev Cell,2021,56(23):3222-3234.e6.DOI: 10.1016/j.devcel.2021.11.008. [19] BonelloTT,ChoiW,PeiferM.Scribble and Discs-large direct initial assembly and positioning of adherens junctions during the establishment of apical-basal polarity[J].Development,2019,146(22):dev180976.DOI: 10.1242/dev.180976. [20] ChungS,KimS,AndrewDJ.Uncoupling apical constriction from tissue invagination[J].Elife,2017,6:e22235.DOI: 10.7554/eLife.22235. [21] KaiY.Mechanical regulation of tissues that reproduces wrinkle patterns of gastrointestinal tracts[J].Phys Biol,2022,19(3).DOI: 10.1088/1478-3975/ac6042. [22] MotaB,Herculano-HouzelS.BRAIN STRUCTURE. Cortical folding scales universally with surface area and thickness, not number of neurons[J].Science,2015,349(6243):74-77.DOI: 10.1126/science.aaa9101. [23] VerkhovskyAB,SvitkinaTM,BorisyGG.Self-polarization and directional motility of cytoplasm[J].Curr Biol,1999,9(1):11-20.DOI: 10.1016/s0960-9822(99)80042-6. [24] WeberGF,BjerkeMA,DeSimoneDW.A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration[J].Dev Cell,2012,22(1):104-115.DOI: 10.1016/j.devcel.2011.10.013. [25] ParsonsTT,MosallaeiS,RafteryLA.Two phases for centripetal migration of Drosophila melanogaster follicle cells: initial ingression followed by epithelial migration[J].Development,2023,150(6):dev200492.DOI: 10.1242/dev.200492. [26] CaiD,ChenSC,PrasadM,et al.Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration[J].Cell,2014,157(5):1146-1159.DOI: 10.1016/j.cell.2014.03.045. [27] VilledieuA,BosveldF,BellaïcheY.Mechanical induction and competence in epithelial morphogenesis[J].Curr Opin Genet Dev,2020,63:36-44.DOI: 10.1016/j.gde.2020.03.003. [28] Chiasson-MacKenzieC,MorrisZS,BacaQ,et al.NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin[J].J Cell Biol,2015,211(2):391-405.DOI: 10.1083/jcb.201503081. [29] JebeliM,LopezSK,GoldblattZE,et al.Multicellular aligned bands disrupt global collective cell behavior[J].Acta Biomater,2023,163:117-130.DOI: 10.1016/j.actbio.2022.10.041. [30] KonjarŠ, PavšičM, VeldhoenM. Regulation of oxygen homeostasis at the intestinal epithelial barrier site[J]. Int J Mol Sci, 2021, 22(17):9170.DOI: 10.3390/ijms22179170. [31] SalviAM,BaysJL,MackinSR,et al.Ankyrin G organizes membrane components to promote coupling of cell mechanics and glucose uptake[J].Nat Cell Biol,2021,23(5):457-466.DOI: 10.1038/s41556-021-00677-y. [32] ParkJS,BurckhardtCJ,LazcanoR,et al.Mechanical regulation of glycolysis via cytoskeleton architecture[J].Nature,2020,578(7796):621-626.DOI: 10.1038/s41586-020-1998-1. [33] HuH, JuvekarA, LyssiotisCA, et al. Phosphoinositide 3-kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton[J]. Cell, 2016, 164(3): 433-446.DOI: 10.1016/j.cell.2015.12.042. [34] BaysJL,CampbellHK,HeidemaC,et al.Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK[J].Nat Cell Biol,2017,19(6):724-731.DOI: 10.1038/ncb3537. [35] MiceliC,RoccioF,Penalva-MoussetL,et al.The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells[J].Nat Cell Biol,2020,22(9):1091-1102.DOI: 10.1038/s41556-020-0566-0. [36] TharpKM,Higuchi-SanabriaR,TimblinGA,et al.Adhesion-mediated mechanosignaling forces mitohormesis[J].Cell Metab,2021,33(7):1322-1341.e13.DOI: 10.1016/j.cmet.2021.04.017. [37] CaiJ,ChenT,JiangZ,et al.Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma[J].Int J Biol Sci,2023,19(7):2114-2131.DOI: 10.7150/ijbs.82177. [38] EnzoE,SantinonG,PocaterraA,et al.Aerobic glycolysis tunes YAP/TAZ transcriptional activity[J].EMBO J,2015,34(10):1349-1370.DOI: 10.15252/embj.201490379. [39] AngHL,MohanCD,ShanmugamMK,et al.Mechanism of epithelial-mesenchymal transition in cancer and its regulation by natural compounds[J].Med Res Rev,2023,43(4):1141-1200.DOI: 10.1002/med.21948. [40] KoormanT,JansenKA,KhalilA,et al.Spatial collagen stiffening promotes collective breast cancer cell invasion by reinforcing extracellular matrix alignment[J].Oncogene,2022,41(17):2458-2469.DOI: 10.1038/s41388-022-02258-1. [41] HortaCA,DoanK,YangJ.Mechanotransduction pathways in regulating epithelial-mesenchymal plasticity[J].Curr Opin Cell Biol,2023,85:102245.DOI: 10.1016/j.ceb.2023.102245. [42] YuX,HeT,TongZ,et al.Molecular mechanisms of TWIST1-regulated transcription in EMT and cancer metastasis[J].EMBO Rep,2023,24(11):e56902.DOI: 10.15252/embr.202356902. [43] PiccoloS,PancieraT,ContessottoP,et al.YAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches[J].Nat Cancer,2023,4(1):9-26.DOI: 10.1038/s43018-022-00473-z. [44] DupontS,MorsutL,AragonaM,et al.Role of YAP/TAZ in mechanotransduction[J].Nature,2011,474(7350):179-183.DOI: 10.1038/nature10137. [45] YanH,YuCC,FineSA,et al.Loss of the wild-type KRAS allele promotes pancreatic cancer progression through functional activation of YAP1[J].Oncogene,2021,40(50):6759-6771.DOI: 10.1038/s41388-021-02040-9. [46] FanR,KimNG,GumbinerBM.Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1[J].Proc Natl Acad Sci U S A,2013,110(7):2569-2574.DOI: 10.1073/pnas.1216462110. [47] Di-LuoffoM,Ben-MeriemZ,LefebvreP,et al.PI3K functions as a hub in mechanotransduction[J].Trends Biochem Sci,2021,46(11):878-888.DOI: 10.1016/j.tibs.2021.05.005. [48] ScottKE,FraleySI,RangamaniP.A spatial model of YAP/TAZ signaling reveals how stiffness, dimensionality, and shape contribute to emergent outcomes[J].Proc Natl Acad Sci U S A,2021,118(20):e2021571118.DOI: 10.1073/pnas.2021571118. -
Table 1. 通过机械应力参与EMT进程的相关蛋白及其作用机制
类型与蛋白 作用机制 机械传感器 TGF-β1 在高硬度ECM环境中,TGF-β1被激活后促进EMT；在低硬度ECM环境中,TGF-β1会诱导细胞凋亡 MENA 在高硬度ECM环境中,MENA-11a表达下调使乳腺癌细胞侵袭性增加 MGAT5 MGAT5诱导整合素上的N-聚糖分支以形成纤维状环境,使ECM硬度更高,从而促进胶质瘤干细胞迁移 PIEZO2 诱导蛋白激酶B的激活,继而使SNAI1蛋白趋于稳定并发生核转位,从而促进乳腺癌细胞迁移 核骨架与细胞骨架连接复合物 核骨架与细胞骨架连接复合物中的解聚抑制蛋白1和UCN 84结构域1是EMT进程中的必需因子。β-连环蛋白的核转运水平随着UCN 84结构域1的高表达而增加,进而通过效应子级联反应诱导EMT TRPV4 ECM硬度和TGF-β1依赖TRPV4来导致长链非编码RNA和mRNA的差异表达 机械反转录因子 TWIST1 ECM硬度增加可导致TWIST1磷酸化,从而诱导EMT ZEB1 ZEB1通过MGAT5等信号通路来响应ECM硬度变化,以增加N-钙黏蛋白表达,从而诱导EMT SNAI1 在高硬度ECM环境中,整合素连接激酶和SNAI1的表达被上调,整合素连接激酶会促使整合素β1-整合素连接激酶-SNAI1信号通路下游的SNAI1诱导EMT MRTF-A 在高硬度ECM环境中,因细胞骨架重塑和肌动蛋白聚合,MRTF-A被诱导发生核转位从而促进EMT 注：EMT为上皮-间质转化,TGF-β1为转化生长因子β1,MENA为哺乳动物肌动蛋白调节蛋白enabled,MGAT5为甘露糖基-（α-1,6-）-糖蛋白β-1,6-N-乙酰-氨基葡萄糖转移酶5,PIEZO2为压电型机械敏感离子通道组件2,TRPV4为瞬时受体电位香草酸亚型4,TWIST1为扭曲螺旋转录因子1,ZEB1为锌指E-盒结合同源盒蛋白1,SNAI1为蜗牛家族转录抑制因子1,MRTF-A为心肌素相关转录因子A,ECM为细胞外基质 
下载: 导出CSV
-
下载: 
表(1)
计量
- 文章访问数: 280
- HTML全文浏览量: 61
- PDF下载量: 13
- 被引次数: 0
