机构：[1]Liver Transplantation Division, Department of Liver Surgery, West ChinaHospital, Sichuan University, Chengdu, People’s Republic of China[2]Department of Bioengineering and Therapeutic Sciences and Liver Center,University of California, San Francisco, CA, USA[3]Laboratory of Liver Surgery,West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republicof China四川大学华西医院[4]Department of General Surgery, The Second Affiliated Hospital ofXi’an Jiaotong University, Xi’an Jiaotong University, Xi’an, People’s Republic ofChina[5]Institute of Pathology, University of Regensburg, Regensburg, Germany
Dysregulation of transforming growth factor-beta (TGFβ) signaling has been implicated in liver carcinogenesis with both tumor promoting and inhibiting activities. Activation of the c-MYC protooncogene is another critical genetic event in hepatocellular carcinoma (HCC). However, the precise functional crosstalk between c-MYC and TGFβ signaling pathways remains unclear. In the present investigation, we investigated the expression of TGFβ signaling in c-MYC amplified human HCC samples as well as the mechanisms whereby TGFβ modulates c-Myc driven hepatocarcinogenesis during initiation and progression. We found that several TGFβ target genes are overexpressed in human HCCs with c-MYC amplification. In vivo, activation of TGFβ1 impaired c-Myc murine HCC initiation, whereas inhibition of TGFβ pathway accelerated this process. In contrast, overexpression of TGFβ1 enhanced c-Myc HCC progression by promoting tumor cell metastasis. Mechanistically, activation of TGFβ promoted tumor microenvironment reprogramming rather than inducing epithelial-to-mesenchymal transition during HCC progression. Moreover, we identified PMEPA1 as a potential TGFβ1 target. Altogether, our data underline the divergent roles of TGFβ signaling during c-MYC induced HCC initiation and progression.
基金：
NIH grants R01CA190606 and R01CA239251 to
XC, P30DK026743 for UCSF Liver Center, National Natural Science Foundation
of China (grant number 82002967) to HW.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|1 区生物学
小类|2 区细胞生物学
最新[2023]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Liver Transplantation Division, Department of Liver Surgery, West ChinaHospital, Sichuan University, Chengdu, People’s Republic of China[2]Department of Bioengineering and Therapeutic Sciences and Liver Center,University of California, San Francisco, CA, USA[3]Laboratory of Liver Surgery,West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republicof China
通讯作者：
通讯机构：[1]Liver Transplantation Division, Department of Liver Surgery, West ChinaHospital, Sichuan University, Chengdu, People’s Republic of China[3]Laboratory of Liver Surgery,West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republicof China
推荐引用方式(GB/T 7714)：
Wang Haichuan,Wang Pan,Xu Meng,et al.Distinct functions of transforming growth factor-β signaling in c-MYC driven hepatocellular carcinoma initiation and progression.[J].Cell death & disease.2021,12(2):200.doi:10.1038/s41419-021-03488-z.
APA：
Wang Haichuan,Wang Pan,Xu Meng,Song Xinhua,Wu Hong...&Chen Xin.(2021).Distinct functions of transforming growth factor-β signaling in c-MYC driven hepatocellular carcinoma initiation and progression..Cell death & disease,12,(2)
MLA：
Wang Haichuan,et al."Distinct functions of transforming growth factor-β signaling in c-MYC driven hepatocellular carcinoma initiation and progression.".Cell death & disease 12..2(2021):200
生物学