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Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Protein kinase D1 suppresses epithelial-to-mesenchymal transition through phosphorylation of snail

Cheng Du1, Chuanyou Zhang, Sazzad Hassan

  • 1Division of Urology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA. cheng.du@umassmed.edu

Cancer Research
|October 14, 2010
PubMed

Insights

Protein kinase D1 (PKD1) suppresses cancer cell invasion and metastasis by inhibiting epithelial-mesenchymal transition (EMT). Loss of PKD1 promotes aggressive cancer phenotypes, highlighting its role as a tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Epithelial-mesenchymal transition (EMT) drives cancer invasion and metastasis.
  • EMT is associated with increased malignancy and poor prognosis in various cancers.
  • Protein kinase D1 (PKD1) is a kinase implicated in cellular processes, but its role in EMT is unclear.

Purpose of the Study:

  • To investigate the role of protein kinase D1 (PKD1) as a regulator of epithelial-mesenchymal transition (EMT) in cancer.
  • To determine the mechanism by which PKD1 influences EMT and cancer progression.
  • To evaluate PKD1's potential as a therapeutic target for inhibiting cancer metastasis.

Main Methods:

  • Assessed PKD1 expression levels in advanced prostate, breast, and gastric cancer tissues.
  • Utilized ectopic reexpression and small interfering RNA (siRNA) knockdown of PKD1 in cancer cell lines.
  • Investigated PKD1's effect on EMT markers (e.g., E-cadherin, mesenchyme-specific genes).
  • Performed tumor xenograft studies to assess PKD1's impact on tumor growth and metastasis.
  • Examined the phosphorylation of Snail transcription factor by PKD1 and its effect on nuclear export and 14-3-3σ binding.

Main Results:

  • PKD1 expression is downregulated in advanced prostate, breast, and gastric cancers.
  • Reexpression of PKD1 suppressed EMT, reduced mesenchyme markers, and increased epithelial markers.
  • PKD1 knockdown enhanced EMT and mesenchymal characteristics.
  • PKD1 inhibited tumor growth and metastasis in vivo.
  • PKD1 phosphorylates Snail at Ser11, promoting its nuclear export and suppressing EMT.
  • Snail S11 mutation leads to mesenchymal traits and stem cell marker expression.

Conclusions:

  • PKD1 acts as a tumor and metastasis suppressor by inhibiting Snail-mediated EMT.
  • Loss of PKD1 contributes to the acquisition of an aggressive malignant phenotype and metastatic potential.
  • PKD1 represents a potential therapeutic target for overcoming cancer progression and metastasis.

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