Mechanical transmission enables EMT cancer cells to drive epithelial cancer cell migration to guide tumor spheroid disaggregation  

作　　者：Qing Zhang Feng Lin Jianyong Huang Chunyang Xiong 

机构地区：[1]Department of Mechanics and Engineering Science,College of Engineering,Peking University,Beijing 100871,China [2]Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou 325000,China [3]Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Wenzhou 325001,China [4]Beijing Innovation Center for Engineering Science and Advanced Technology,College of Engineering,Peking University,Beijing 100871,China

出　　处：《Science China(Life Sciences)》2022年第10期2031-2049,共19页中国科学（生命科学英文版）

基　　金：supported in part by the National Natural Science Foundation of China (11772006,11972002,11902007);China Postdoctoral Science Foundation (2019M660313)。

摘　　要：Cell phenotype heterogeneity within tumor tissue,especially which due to the emergence of epithelial-mesenchymal transition(EMT) in cancer cells,is associated with cancer invasion and metastasis.However,our understanding of the cellular mechanism(s)underlying the cooperation between EMTcell and epithelial cancer cell migration remains incomplete.Herein,heterotypic tumor spheroids containing both epithelial and EMT cancer cells were generated in vitro.We observed that EMT cells dominated the peripheral region of the self-organized heterotypic tumor spheroid.Furthermore,our results demonstrated that EMT cells could serve as leader cells to improve the collective migration efficiency of epithelial cancer cells and promote dispersion and invasion of the tumor spheroids,which was regulated by the force transition between EMT cells and epithelial cancer cells.Mechanistically,our data further suggest that force transmission is mediated by heterophilic N-cadherin/E-cadherin adhesion complexes between EMT and epithelial cancer cells.Impairment of N-cadherin/E-cadherin adhesion complex formation abrogated the ability of EMT cells to guide epithelial cancer cell migration and blocked the dispersion of tumor spheroids.Together,our data provide new insight into the mechanical interaction between epithelial and EMT cancer cells through heterophilic cadherin adhesion,which enables cooperative tumor cell migration,highlighting the role of EMT cells in tumor invasion.

关 键 词：cancer cell migration traction force E-/N-cadherin mechanics transmission epithelial-mesenchymal transition 

分 类 号：R73-37[医药卫生—肿瘤]