Abstract
Peroxisome proliferator-activated receptor-γ (PPARγ) and retinoic acid X-receptor (RXR) heterodimer, which regulates cell growth and differentiation, represses the TGFβ1 gene that encodes for the protein involved in cancer biology. This review will introduce the novel mechanism associated with the inhibition of the TGFβ1 gene by PPARγ activation, which regulates the dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of TGFβ1 by PPARγ activators can be applied for treating TGFβ1-induced pathophysiologic disorders such as cancer metastasis and fibrosis. In this article, we will discuss the opposing effects of TGFβ on tumor growth and metastasis, and address the signaling pathways regulated by PPARγ for tumor progression and suppression.
Highlights
Peroxisome proliferator-activated receptor-γ (PPARγ) as a ligand-activated transcription factor belongs to the members of nuclear hormone receptor superfamily
A result of our previous study indicated that specific mutations of these nuclear binding sites in the GSTA2 promoter, which are present as a three-peroxisomal proliferator-response element (PPRE) cluster, caused the complete loss of its responsiveness to PPARγ activators [92]
Activation of the PPARγ-retinoic acid X-receptor (RXR) heterodimer represses the TGFβ1 gene through dephosphorylation of a transcription factor called zinc finger transcription factor-9 (Zf9), which has been shown to be induced by phosphatase and tensin homolog deleted on chromosome (PTEN)-mediated p70 ribosomal S6 kinase-1 (S6K1) inhibition [18]
Summary
Peroxisome proliferator-activated receptor-γ (PPARγ) and retinoic acid X-receptor (RXR) heterodimer, which regulates cell growth and differentiation, represses the TGFβ1 gene that encodes for the protein involved in cancer biology. This review will introduce the novel mechanism associated with the inhibition of the TGFβ1 gene by PPARγ activation, which regulates the dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of TGFβ1 by PPARγ activators can be applied for treating TGFβ1-induced pathophysiologic disorders such as cancer metastasis and fibrosis. We will discuss the opposing effects of TGFβ on tumor growth and metastasis, and address the signaling pathways regulated by PPARγ for tumor progression and suppression
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