Down-regulation of programmed cell death 4 leads to epithelial to mesenchymal transition and promotes metastasis in mice

Qing Wang, Jiang Zhu, Yong Zhang, Zhenxiao Sun, Xiaoling Guo, Xin Wang, Eun Lee, Vasudevan Bakthavatchalu, Qifeng Yang, Hsin Sheng Yang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

In this study, we demonstrated that knockdown of programmed cell death 4 (Pdcd4), a novel tumour suppressor, decreased the expressions of epithelial-specific proteins and increased the expressions of mesenchymal-specific proteins in vitro and in vivo, suggesting that knockdown of Pdcd4 results in epithelial to mesenchymal transition (EMT). Knockdown of Pdcd4 increased the rate of wound closure and migration capacity in wound-healing assays and Boyden chamber migration assays, respectively, indicating that Pdcd4 knockdown promotes cell migration. Pdcd4 knockdown also altered the adhesion capacity of GEO cells to extracellular matrix including laminin, collagen IV and fibronectin. To test whether knockdown of Pdcd4 promotes metastasis in vivo, parental, control and Pdcd4 knockdown cells were injected into the caecal wall (orthotopic implantation) of nude mice. Tumours are formed on caecum in all injected mice. However, only mice injected with Pdcd4 knockdown cells developed hepatic and local lymph node metastases. Immunohistochemical staining analyses showed that c-Myc and Snail/Slug expressions were up-regulated in the tumours derived from injection of Pdcd4 knockdown cells. These results implicated that promotion of metastasis by Pdcd4 knockdown was contributed by up-regulation of c-Myc and Snail/Slug in nude mice. Taken together, our data demonstrated that knockdown of Pdcd4 leads to EMT, alternation of adhesion and promotion of migration and metastasis.

Original languageEnglish
Pages (from-to)1761-1770
Number of pages10
JournalEuropean Journal of Cancer
Volume49
Issue number7
DOIs
StatePublished - May 2013

Bibliographical note

Funding Information:
We greatly thank Dr. Daret St. Clair and Mrs. Heather Russell-Simmons for reading this manuscript and Ms. Yan Zhang for her technical assistance. This study was supported by a National Institute of Health Grant (RO1CA129015).

Keywords

  • Colon cancer
  • EMT
  • Metastasis
  • Migration
  • Orthotopic implantation
  • Pdcd4

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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