Gene expression of the lysophosphatidic acid receptor 1 is a target of transforming growth factor beta.

ABSTRACT: The lysophosphatidic acid (LPA) receptor LPA1/Edg2 is the first identified LPA receptor. Although its wide tissue distribution and biological functions have been well studied, little is known about how LPA1 is transcriptionally regulated. In the current study, we showed that LPA1 is a physiological target of transforming growth factor beta (TGFβ)-mediated repression. In both normal and neoplastic cells, TGFβ inhibits LPA1 promoter activity, LPA1 mRNA expression and LPA1-dependent chemotaxis and tumor cell invasion. Knockdown of the TGFβ intracellular effector Smad3 or Smad4 with lentivirally transduced short hairpin RNA relieved these inhibitory effects of TGFβ. Interestingly, the LPA1 promoter contains two potential TGFβ inhibitory elements (TIEs), each consisting of a Smad-binding site a

SUBMITTER: Wu J 

PROVIDER: S-EPMC3480976 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature