The roles of FOXM1 in pancreatic stem cells and carcinogenesis

Mol Cancer. 2013 Dec 10;12:159. doi: 10.1186/1476-4598-12-159.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses among all cancers. Over the past several decades, investigators have made great advances in the research of PDAC pathogenesis. Importantly, identification of pancreatic cancer stem cells (PCSCs) in pancreatic cancer cases has increased our understanding of PDAC biology and therapy. PCSCs are responsible for pancreatic tumorigenesis and tumor progression via a number of mechanisms, including extensive proliferation, self-renewal, high tumorigenic ability, high propensity for invasiveness and metastasis, and resistance to conventional treatment. Furthermore, emerging evidence suggests that PCSCs are involved in the malignant transformation of pancreatic intraepithelial neoplasia. The molecular mechanisms that control PCSCs are related to alterations of various signaling pathways, for instance, Hedgehog, Notch, Wnt, B-cell-specific Moloney murine leukemia virus insertion site 1, phosphoinositide 3-kinase/AKT, and Nodal/Activin. Also, authors have reported that the proliferation-specific transcriptional factor Forkhead box protein M1 is involved in PCSC self-renewal and proliferation. In this review, we describe the current knowledge about the signaling pathways related to PCSCs and the early stages of PDAC development, highlighting the pivotal roles of Forkhead box protein M1 in PCSCs and their impacts on the development and progression of pancreatic intraepithelial neoplasia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Proliferation
  • Cell Transformation, Neoplastic*
  • Disease Progression
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / metabolism
  • Forkhead Transcription Factors / physiology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Signal Transduction

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors