Regulation of E-cadherin expression by Poly(ADP-ribosyl)ation during Development and Tumorigenesis. Yingbiao Ji, Alexei Tulin. Cancer Biology Program, Fox Chase Cancer Ctr, Philadelphia, PA.

   Metastatic prostate cancer is a leading cause of cancer death due to resistance to the androgen deprivation therapy in the male population in USA. E-cadherin expression induces an epithelial-mesenchymal transition within tumor cells to promote prostate cancer metastasis. We have found that Drosophila HnRNP A1(Hrp38) binds to the 5UTR of E-cadherin mRNA to control its translation likely by an IRES (Internal Ribosome Entry Site)-mediated process. Hrp38 loss-of-function causes oocyte mislocalization and loss of GSC self-renewal ability due to decreased E-cahderin expression. In contrast, the accumulation of poly(ADP-ribose) in the progenitor cells disrupts the interaction of Hrp38 with the 5UTR of E-cadherin mRNA, decreasing E-cadherin expression. Therefore, hnRNP poly(ADP-ribosyl)ation regulates E-cadherin translation during Drosophila oogenesis. We are exploring if poly(ADP-ribose) also controls E-cadherin expression levels through the same mechanism during tumor metastasis. Our preliminary data demonstrates that the prostate cancer cell lines overexpress PARP1, a pattern that is associated with significantly reduced Parg and E-cadherin expression compared to the wild-type prostate cell lines. This result suggests that regulation of E-cadherin expression by poly(ADP-ribosyl)ation may be conserved between Drosophila and mammals.