title: TGF-β cascade regulation by PPP1 and its interactors -impact on prostate cancer development and therapy.
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.
authors.affiliation: Signal Transduction Laboratory, Centre for Cell Biology, Biology Department, Health Sciences Department, University of Aveiro, Aveiro, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Korrodi-Gregório
authors.forename: Joana Vieira
authors.initials: JV
authors.lastname: Silva
authors.forename: Luís
authors.initials: L
authors.lastname: Santos-Sousa
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Freitas
authors.forename: Juliana
authors.initials: J
authors.lastname: Felgueiras
authors.forename: Margarida
authors.initials: M
authors.lastname: Fardilha
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D055412:Growth Differentiation Factors / Q000235:genetics; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D055412:Growth Differentiation Factors; D016212:Transforming Growth Factor beta; C517187:PPP1CA protein, human; D054645:Protein Phosphatase 1
keywords: PIP; PPP1; TGF-β; phosphatase; prostate cancer; signal transduction therapy