Multiple roles of mothers against decapentaplegic homolog 4 in tumorigenesis, stem cells, drug resistance, and cancer therapy  

作　　者：Chuan-Jing Dai Yu-Ting Cao Fang Huang Yi-Gang Wang 

机构地区：[1]College of Life Sciences and Medicine,Zhejiang Sci-Tech University,Hangzhou 310018,Zhejiang Province,China [2]Department of Pathology,Zhejiang Provincial People’s Hospital of Hangzhou Medical University,Hangzhou 310014,Zhejiang Province,China

出　　处：《World Journal of Stem Cells》2022年第1期41-53,共13页世界干细胞杂志（英文版）（电子版）

基　　金：the National Natural Science Foundation of China,No.8180306;the Natural Science Foundation of Zhejiang Province,No.LY18C070002;the 521 Talent Project of Zhejiang Sci-Tech University,No.2021437620 and No.2019337459.

摘　　要：The transforming growth factor(TGF)-βsignaling pathway controls many cellular processes,including proliferation,differentiation,and apoptosis.Abnormalities in the TGF-βsignaling pathway and its components are closely related to the occurrence of many human diseases,including cancer.Mothers against decapentaplegic homolog 4(Smad4),also known as deleted in pancreatic cancer locus 4,is a typical tumor suppressor candidate gene locating at q21.1 of human chromosome 18 and the common mediator of the TGF-β/Smad and bone morphogenetic protein/Smad signaling pathways.It is believed that Smad4 inactivation correlates with the development of tumors and stem cell fate decisions.Smad4 also interacts with cytokines,miRNAs,and other signaling pathways,jointly regulating cell behavior.However,the regulatory function of Smad4 in tumorigenesis,stem cells,and drug resistance is currently controversial.In addition,Smad4 represents an attractive therapeutic target for cancer.Elucidating the specific role of Smad4 is important for understanding the mechanism of tumorigenesis and cancer treatment.Here,we review the identification and characterization of Smad4,the canonical TGF-β/Smad pathway,as well as the multiple roles of Smad4 in tumorigenesis,stem cells,and drug resistance.Furthermore,we provide novel insights into the prospects of Smad4-targeted cancer therapy and the challenges that it will face in the future.

关 键 词：Cancer therapy Drug resistance Mothers against decapentaplegic homolog 4 STEMNESS Transforming growth factor-β TUMORIGENESIS 

分 类 号：R730.5[医药卫生—肿瘤]