2. Academic Validation
  3. PLAGL2 promotes epithelial-mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1

PLAGL2 promotes epithelial-mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1

  • Br J Cancer. 2020 Feb;122(4):578-589. doi: 10.1038/s41416-019-0679-z.
Liang Wu 1,  Zili Zhou 1,  Shengbo Han 1,  Jinhuang Chen 2,  Zhengyi Liu 1,  Xudan Zhang 1,  Wenzheng Yuan 3,  Jintong Ji 4,  Xiaogang Shu 5
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 4 Department of Gastrointestinal Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 5 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected].
PMID: 31827238 DOI: 10.1038/s41416-019-0679-z
Abstract

Background: We previously demonstrated that the pleomorphic adenoma gene like-2 (PLAGL2) is involved in the pathogenesis of Hirschsprung disease. Enhanced PLAGL2 expression was observed in several malignant tumours. However, the exact function of PLAGL2 and its underlying mechanism in colorectal Cancer (CRC) remain largely unknown.

Methods: Immunohistochemical analysis of PLAGL2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of PLAGL2 in the progression of CRC.

Results: Enhanced PLAGL2 expression was significantly associated with EMT-related proteins in CRC. The data revealed that PLAGL2 promotes CRC cell proliferation, migration, invasion and EMT both in vitro and in vivo. Mechanistically, PLAGL2 promoted the expression of ZEB1. PLAGL2 enhanced the expression and nuclear translocation of β-catenin by decreasing its phosphorylation. The depletion of β-catenin neutralised the regulation of ZEB1 that was caused by enhanced PLAGL2 expression. The small-molecule inhibitor PNU-74654, also impaired the enhancement of ZEB1 that resulted from the modified PLAGL2 expression. The depletion of ZEB1 could block the biological function of PLAGL2 in CRC cells.

Conclusions: Collectively, our findings suggest that PLAGL2 mediates EMT to promote colorectal Cancer metastasis via β-catenin-dependent regulation of ZEB1.

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