2. Academic Validation
  3. Up-regulation of Dsg2 confered stem cells with malignancy through wnt/β-catenin signaling pathway

Up-regulation of Dsg2 confered stem cells with malignancy through wnt/β-catenin signaling pathway

  • Exp Cell Res. 2022 Nov 11;422(1):113416. doi: 10.1016/j.yexcr.2022.113416.
Ling Chen 1,  Yanxia Liu 2,  Yanning Xu 3,  Said M Afify 4,  Ang Gao 5,  Juan Du 6,  Bingbing Liu 1,  Xiaoying Fu 6,  Yixin Liu 1,  Ting Yan 7,  Zhengmao Zhu 8,  Masaharu Seno 9
Affiliations

Affiliations

  • 1 Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Gynecology Obstetrics Hospital of Nankai University, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin, 300100, PR China.
  • 2 Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Gynecology Obstetrics Hospital of Nankai University, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin, 300100, PR China; Department of Pathology, Jiangyin People's Hospital, Affiliated Jiangyin Hospital of the Southeast University Medical College, Jiangyin, 214400, PR China.
  • 3 Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Gynecology Obstetrics Hospital of Nankai University, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin, 300100, PR China; Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan; Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan.
  • 4 Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan; Division of Biochemistry, Chemistry Department, Faculty of Science, Menoufia University, Shebin El Koum-Menoufia 32511, Egypt.
  • 5 Department of Genetics and Cell Biology, College of Life Science, Nankai University, Tianjin, 300071, PR China.
  • 6 Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan; Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan.
  • 7 Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer, Shanxi Medical University, Taiyuan, 030001, PR China.
  • 8 Department of Genetics and Cell Biology, College of Life Science, Nankai University, Tianjin, 300071, PR China. Electronic address: zhuzhengmao@naikai.edu.cn.
  • 9 Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan; Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan; Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic & Research, Okayama University, Okayama, 700-8530, Japan. Electronic address: mseno@okayama-u.ac.jp.
PMID: 36375513 DOI: 10.1016/j.yexcr.2022.113416
Abstract

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.

Keywords

Cancer stem cells; Dsg2; Malignant conversion; Wnt/β-catenin signaling pathway; miPS.

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