TGF-β cascade regulation by PPP1 and its interactors -impact on prostate cancer development and therapy

J Cell Mol Med. 2014 Apr;18(4):555-67. doi: 10.1111/jcmm.12266. Epub 2014 Mar 15.

Abstract

Protein phosphorylation is a key mechanism by which normal and cancer cells regulate their main transduction pathways. Protein kinases and phosphatases are precisely orchestrated to achieve the (de)phosphorylation of candidate proteins. Indeed, cellular health is dependent on the fine-tune of phosphorylation systems, which when deregulated lead to cancer. Transforming growth factor beta (TGF-β) pathway involvement in the genesis of prostate cancer has long been established. Many of its members were shown to be hypo- or hyperphosphorylated during the process of malignancy. A major phosphatase that is responsible for the vast majority of the serine/threonine dephosphorylation is the phosphoprotein phosphatase 1 (PPP1). PPP1 has been associated with the dephosphorylation of several proteins involved in the TGF-β cascade. This review will discuss the role of PPP1 in the regulation of several TGF-β signalling members and how the subversion of this pathway is related to prostate cancer development. Furthermore, current challenges on the protein phosphatases field as new targets to cancer therapy will be addressed.

Keywords: PIP; PPP1; TGF-β; phosphatase; prostate cancer; signal transduction therapy.

Publication types

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

MeSH terms

  • Carcinogenesis / genetics*
  • Extracellular Matrix / metabolism
  • Growth Differentiation Factors / genetics
  • Humans
  • Male
  • Phosphorylation
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Phosphatase 1 / metabolism*
  • Signal Transduction / genetics
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism

Substances

  • Growth Differentiation Factors
  • Transforming Growth Factor beta
  • PPP1CA protein, human
  • Protein Phosphatase 1