The role of DJ-1, a PTEN inhibitor, and sodium 4-phenyl butyrate in cancer cell motility and metastasis

Abstract

Dj-1 is a dimeric protein with a molecular weight of 20KD. It was originally discovered in Parkinson disease by Nakagubo et al (1997). The Dj-1 protein was implicated in many diseases that are cancer related. In 2005, Dj-1 was found to be an inhibitor of the tumor suppressor PTEN and thus a regulator of the PI3Kinase pathway. By inhibiting PTEN, Dj-1 allows the production of PIP3 through the activation of PI3K leading to constant cell proliferation. Based on the above we tested the role of Dj-1 in cancer cell motility and metastasis. Results show that both the loss and gain of Dj-1 lead to a decrease in cancer cell motility. Dj-1 knockdown through siRNA transfection led to a decrease in cell motility. In addition sodium-4-phenyl butyrate (PBA), known to increase the expression of Dj-1 by binding to its sp-1binding domain, led to reduced cell motility. In vivo tail vein injection of melanoma cell as in black mice and treatment with PBA confirmed the in vitro studies, where animals treated with the drugs had less metastasis to the lungs. This introduces PBA as a potential therapeutic drug for cell metastasis.