Alterations in TGFβ signaling during prostate cancer progression.
Bethtrice Thompson-Elliott, Rarnice Johnson, Shafiq A. Khan
Abstract
During prostate cancer progression, TGF-β acts as both a tumor suppressor and tumor promoter. TGF-β inhibits cell proliferation in normal and early-stage prostate cancer cells, but during later stages of the disease the cancer cells develop resistance to inhibitory effects on cell proliferation. In these cells, TGF-β promotes cancer progression due to its effects on epithelial to mesenchymal transition (EMT), cell migration and invasion, and immune suppression. The intracellular mechanisms involved in the development of resistance to TGF-β effects on cell proliferation are largely unknown. In this review, we summarized the roles of several intracellular proteins including PTEN, Id1 and JunD, which may play a role in this transition. The role of Ski/SnoN proteins in inhibition of Smad2/3 signaling is highlighted.