PDK1: At the crossroad of cancer signaling pathways

Semin Cancer Biol. 2018 Feb:48:27-35. doi: 10.1016/j.semcancer.2017.04.014. Epub 2017 May 1.

Abstract

Rational target therapy of cancer would benefit from the identification of new targets that can be easily inhibited by small molecules. An increasing amount of evidence hints at 3-phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1) as an intriguing and underexplored target for cancer therapy. Several reports show that PDK1 expression is dysregulated in multiple cancer types. Furthermore PDK1 is implicated in signaling pathways frequently altered in cancer, such as PI3K/Akt, Ras/MAPK and Myc. PDK1 targeting has been proven to be effective in experimental models harboring alterations of these pathways. In this paper we review PDK1 main biochemical mechanisms, its alterations in cancer and interactions with relevant cancer pathways. A potential role of PDK1 in tumor microenvironment is also discussed.

Keywords: Myc; PDPK1; PI3K/Akt; Ras/MAPK; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genes, myc
  • Humans
  • MAP Kinase Signaling System
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Signal Transduction
  • Tumor Microenvironment
  • ras Proteins / metabolism

Substances

  • PDK1 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Protein Serine-Threonine Kinases
  • ras Proteins