TY - JOUR
T1 - Up-regulation of Dsg2 confered stem cells with malignancy through wnt/β-catenin signaling pathway
AU - Chen, Ling
AU - Liu, Yanxia
AU - Xu, Yanning
AU - Afify, Said M.
AU - Gao, Ang
AU - Du, Juan
AU - Liu, Bingbing
AU - Fu, Xiaoying
AU - Liu, Yixin
AU - Yan, Ting
AU - Zhu, Zhengmao
AU - Seno, Masaharu
N1 - Funding Information:
The study was supported by National Natural Science Foundation of China , Yong Scientists Fund (Grant No. 81402320 ), National Natural Science Foundation of China (Grant No. 91649107 ), Natural Science Foundation of Tianjin City , China (Grant No. 17JCYBJC24100 and 16JCYBJC27000 ), Tianjin Municipal Bureau of Public Health , China ( MS20021 ) and Tianjin Key Medical Discipline (Specialty) Construction Project ( TJYXZDXK-043A ).
Publisher Copyright:
© 2022 The Authors
PY - 2023/1/1
Y1 - 2023/1/1
N2 - In the previous study, we originally developed cancer stem cells (CSCs) models from mouse induced pluripotent stem cells (miPSCs) by culturing miPSCs in the conditioned medium of cancer cell lines, which mimiced as carcinoma microenvironment. However, the molecular mechanism of conversion in detail remains to be uncovered. Microarray analysis of the CSCs models in this study revealed Dsg2, one of the members of the desmosomal cadherin family, was up-regulated when compared with the original miPSCs. Moreover, the expression of key factors in Wnt/β-catenin signaling pathway were also found up-regulated in one of the CSCs models, named miPS-LLCcm. An autocrine loop was implied between Dsg2 and Wnt/β-catenin signaling pathway when miPSCs were treated with Wnt/β-catenin signaling pathway activators, Wnt3a and CHIR99021, and when the CSCs model were treated with inhibitors, IWR-1 and IWP-2. Furthermore, the ability of proliferation and self-renewal in the CSCs model was markedly decreased in vitro and in vivo when Dsg2 gene was knocked down by shRNA. Our results showed that the Wnt/β-catenin signaling pathway is activated by the up-regulation of Dsg2 expresssion during the conversion of miPSCs into CSCs implying a potential mechanism of the tranformation of stem cells into malignant phenotype.
AB - In the previous study, we originally developed cancer stem cells (CSCs) models from mouse induced pluripotent stem cells (miPSCs) by culturing miPSCs in the conditioned medium of cancer cell lines, which mimiced as carcinoma microenvironment. However, the molecular mechanism of conversion in detail remains to be uncovered. Microarray analysis of the CSCs models in this study revealed Dsg2, one of the members of the desmosomal cadherin family, was up-regulated when compared with the original miPSCs. Moreover, the expression of key factors in Wnt/β-catenin signaling pathway were also found up-regulated in one of the CSCs models, named miPS-LLCcm. An autocrine loop was implied between Dsg2 and Wnt/β-catenin signaling pathway when miPSCs were treated with Wnt/β-catenin signaling pathway activators, Wnt3a and CHIR99021, and when the CSCs model were treated with inhibitors, IWR-1 and IWP-2. Furthermore, the ability of proliferation and self-renewal in the CSCs model was markedly decreased in vitro and in vivo when Dsg2 gene was knocked down by shRNA. Our results showed that the Wnt/β-catenin signaling pathway is activated by the up-regulation of Dsg2 expresssion during the conversion of miPSCs into CSCs implying a potential mechanism of the tranformation of stem cells into malignant phenotype.
KW - Cancer stem cells
KW - Dsg2
KW - Malignant conversion
KW - miPS
KW - Wnt/β-catenin signaling pathway
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U2 - 10.1016/j.yexcr.2022.113416
DO - 10.1016/j.yexcr.2022.113416
M3 - Article
C2 - 36375513
AN - SCOPUS:85142751075
SN - 0014-4827
VL - 422
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
M1 - 113416
ER -
