A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition

Cell Adh Migr. 2015;9(4):317-24. doi: 10.1080/19336918.2015.1016686. Epub 2015 Aug 4.

Abstract

Tumor metastasis is not only a sign of disease severity but also a major factor causing treatment failure and cancer-related death. Therefore, studies on the molecular mechanisms of tumor metastasis are critical for the development of treatments and for the improvement of survival. The epithelial-mesenchymal transition (EMT) is an orderly, polygenic biological process that plays an important role in tumor cell invasion, metastasis and chemoresistance. The complex, multi-step process of EMT involves multiple regulatory mechanisms. Specifically, the PI3K/Akt signaling pathway can affect the EMT in a variety of ways to influence tumor aggressiveness. A better understanding of the regulatory mechanisms related to the EMT can provide a theoretical basis for the early prediction of tumor progression as well as targeted therapy.

Keywords: CK, cytokeratin; ECM, extracellular matrix; EMT; EMT, epithelial-mesenchymal transition; FGF, fibroblast growth factor; GSK-3β, glycogen synthase kinase 3 β; ILK, integrin-linked kinase; MDR, multidrug resistance; MET, mesenchymal-epithelial transition; PDGF, platelet-derived growth factor; PDK1, 3-phosphoinositide-dependent protein kinase 1; PI3K, phosphatidylinositol-3-kinase; PI3K/Akt signaling pathway; PKA, protein kinase A; PKB, protein kinase B; PKC, protein kinase C; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α; YB-1, Y-box binding protein-1; anti-cancer therapy; bHLH, basic helix-loop-helix protein; extracellular matrix; transcription factors; tumor aggressiveness.

Publication types

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

MeSH terms

  • Animals
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology*
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt