Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells

Cancer Lett. 2013 Oct 28;340(1):113-23. doi: 10.1016/j.canlet.2013.07.009. Epub 2013 Jul 17.

Abstract

Pancreatic cancer is notorious for its difficult diagnosis at early stage and poor recurrence-free prognosis. This study aimed to investigate the possible involvement of Oct4 and Nanog in pancreatic cancer. The high expressions of Oct4 and Nanog in human pancreatic cancer tissues were found to indicate a worse prognostic value of patients. The pancreatic cancer stem cells (PCSCs) that isolated from PANC-1 cell line by flow cytometry exhibited high expressions of Oct4 and Nanog. To investigate whether Oct4 and Nanog play crucial role in maintaining the stemness of PCSCs, double knockdown of Oct4 and Nanog demonstrated that Oct4 and Nanog significantly reduced proliferation, migration, invasion, chemoresistance, and tumorigenesis of PCSCs in vitro and in vivo. The altered expression of the genes related to pancreatic carcinogenesis, metastasis, drug resistance and epithelial-mesenchymal transdifferentiation (EMT) might affect the biological characteristics of PCSCs. Our results suggest that Oct4 and Nanog may serve as a potential marker of prognosis and a novel target of therapy for pancreatic cancer.

Keywords: Cancer stem cells; Nanog; Oct4; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Drug Resistance, Neoplasm
  • Female
  • Gemcitabine
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanog Homeobox Protein
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / physiology*
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • RNA Interference
  • Tumor Burden

Substances

  • Antimetabolites, Antineoplastic
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Deoxycytidine
  • Gemcitabine