title: Down-regulation of programmed cell death 4 leads to epithelial to mesenchymal transition and promotes metastasis in mice.
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.
authors: Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors: Qing
authors: Q
authors: Wang
authors: Jiang
authors: J
authors: Zhu
authors: Yong
authors: Y
authors: Zhang
authors: Zhenxiao
authors: Z
authors: Sun
authors: Xiaoling
authors: X
authors: Guo
authors: Xin
authors: X
authors: Wang
authors: Eun
authors: E
authors: Lee
authors: Vasudevan
authors: V
authors: Bakthavatchalu
authors: Qifeng
authors: Q
authors: Yang
authors: Hsin-Sheng
authors: HS
authors: Yang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D051017:Apoptosis Regulatory Proteins; C498443:Pdcd4 protein, mouse; D020598:Proto-Oncogene Proteins c-myb; D016601:RNA-Binding Proteins; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors