Figure 7.

Hypothetical working model of LPA-induced A431 colony dispersal. We hypothesize that LPA induces Ln-332 expression via TGF-β1 pathway. In our working model, LPA binds to LPA receptors on the A431 cell surface and transactivates TGF-β1 type I receptor (TGFβR1), which phosphorylates receptor-regulated Smad (R-Smad), Smad2, and Smad3. These results are supported by other previous findings [36, 40, 41]. Another potential pathway may lead to the direct induction of phosphorylation of Smad2/3.Phosphorylated Smad2/3 forms complex with Smad4 and translocates into the nucleus [41]. Smad4 functions as a positive transcriptional regulator of Ln-332 [42]. Finally, LPA enhances Ln-332 expression to promote A431 colony dispersal.