The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer.Here,we report that esophageal squamous cell carcinoma(ESCC)cells display molecular features equally similar...The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer.Here,we report that esophageal squamous cell carcinoma(ESCC)cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells,which we term as confused cell identity(CCI).CCI is an independent prognostic marker associated with poor prognosis in ESCC.Further,we identify tropomyosin 4(TPM4)as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo.And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway.Thus,our study suggests an unrecognized feature of ESCC cells,which might be of value for clinic prognosis and potential interference.展开更多
基金supported by the Key Technology Research and Development Program of Zhejiang Province [No.2017C03017]the National Natural Science Foundation of China [81672916,11932017,81802750]+2 种基金the Natural Science Foundation of Zhejiang Province [LQ20H180014 to Y.Y.]the China Postdoctoral Science Foundation [2019M652117 to Y.Y.]the Natural Science Foundation of Zhejiang Province [LBY20H160002].
基金We thank the members of the CC-LY laboratory for their technical support and suggestions,and the Core Facilities of West China Hospital.This work was supported by the National Key R&D Program of China(2017YFA0505600)the National Natural Science Foundation of China(81522003,82170171,81770157,and 82003156)+1 种基金the Sichuan Science and Technology Program(2020YFQ0059,2018JZ0077,2017TJPT0005,2022YFS0171 and 2022YFS0205)1.3.5.Project for Disciplines of Excellence,West China Hospital,Sichuan University,and the innovation initiative of Sichuan University,Grant no.2018SCUH0060.We thank the Chengdu OrganoidMed Medical Laboratory for their technical support.We also thank BioRender(biorender.com)for providing items for drawing scheme graphs.
文摘The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer.Here,we report that esophageal squamous cell carcinoma(ESCC)cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells,which we term as confused cell identity(CCI).CCI is an independent prognostic marker associated with poor prognosis in ESCC.Further,we identify tropomyosin 4(TPM4)as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo.And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway.Thus,our study suggests an unrecognized feature of ESCC cells,which might be of value for clinic prognosis and potential interference.