Prolonged overexpression of Wnt10b induces epidermal keratinocyte transformation through activating EGF pathway

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• 作者：Mingxing Lei ; Xiangdong Lai ; Xiufeng Bai ; Weiming Qiu…
• 关键词：Wnt10b ; DKK1 ; Epidermal keratinocyte ; JB6 cell ; Tumorigenesis
• 刊名：Histochemistry and Cell Biology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：144
• 期：3
• 页码：209-221
• 全文大小：4,389 KB
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• 作者单位：Mingxing Lei (1)
  Xiangdong Lai (1)
  Xiufeng Bai (1)
  Weiming Qiu (1)
  Tian Yang (1)
  Xiaoling Liao (4)
  Cheng-Ming Chuong (5)
  Li Yang (2) (3)
  Xiaohua Lian (1)
  Julia Li Zhong (2) (3)
  
  1. Department of Cell Biology, the Third Military Medical University, Chongqing, 400038, People’s Republic of China
  4. Institute of Biomedical Engineering, Chongqing University of Science and Technology, Chongqing, 401331, People’s Republic of China
  5. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  2. Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People’s Republic of China
  3. -11-Project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, 400044, People’s Republic of China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Anatomy
  Medicine/Public Health, general
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-119X

文摘

Wnt10b is a signaling protein regulating skin development and homeostasis, and the expression of Wnt10b is restricted to epidermal keratinocytes in embryonic and postnatal skin. Recent studies indicate an elevated expression of Wnt10b in skin tumors. However, how Wnt10b regulates skin tumorigenesis remains largely unknown. Here we report that continuous expression of Wnt10b mediates transformation of epidermal keratinocytes through activating genes involved in EGF/MAPK signaling pathways. We first established a prolonged Wnt10b overexpression system in JB6P?cells to represent the elevated Wnt10b expression level in skin keratinocytes. Through expression assays and observations under phase-contrast microscopy, prolonged expression of Wnt10b activated Wnt/β-catenin pathway and induced morphological changes of cells showing longer protrusions and multilayer growth, indicating early-stage cell transformation. Wnt10b also increased cellular proliferation and migration according to BrdU incorporation and cell mobility assays. Furthermore, multi-doses of AdWnt10b treatment to JB6P?cells induced colony formation, stronger invasive ability in transwell system, and anchorage-independent growth in agar gel. In molecular level, AdWnt10b treatment induced increased transcriptional expressions of Egf, downstream Mapk pathway factors, and MMPs. Administration of Wnt antagonist DKK1 blocked the tumor promotion process induced by Wnt10b. Taken together, these findings clearly demonstrate that Wnt10b promotes epidermal keratinocyte transformation through induced Egf pathway.