TUMOR-ASSOCIATED FIBROBLASTS SUPPRESS ZINC FINGER PROTEIN EXPRESSION TO PROMOTE THE PROSTATE CANCER PROGRESSION THROUGH TYROSINE PHOSPHATASE/PY-STAT SIGNALING.

Prostate cancer remains the most commonly diagnosed cancer in male, and despite recent advances in treatment patients with metastatic disease continue to have poor survival rates. Although prostate cancer is clinically manageable during several stages of progression, metastatic progression severely compromised the prognosis and leads to mortality. Recent studies have revealed the critical role of the tumor microenvironment and progression of advanced disease in prostate cancer. Metastatic prostate cancer is affected by the tumor microenvironment, especially fibroblasts around the cancer. We found that activated fibroblasts secrete the chemokine A, which makes prostate cancer more aggressive and inhibits zinc finger protein expression. Here, we examined how zinc finger protein plays a role in metastatic prostate cancer, which is exacerbated by fibroblast. G0/G1 cell cycle arrest, cell apoptosis, cell migration and invasion of prostate cancer cells were attenuated by the zinc finger protein expression. Mechanistically, we demonstrated a novel role of zinc finger protein as a transcriptional regulator of the Tyrosine phosphatase that inhibits oncogenic JAK/STAT pathway. Furthermore, we evaluated zinc finger protein, tyrosine phosphatase and STAT expression levels in a panel of prostate cancer Tissue microarray (TMA) containing patient samples from primary and metastatic sites by immunohistochemistry (IHC).  As the results, compared with the normal (benign) prostate, high-grade prostate cancer patient tissue was negative correlated with zinc finger protein expression. These results suggest that the collapse of zinc finger protein expression by the chemokine A derived from fibroblasts stimulates prostate cancer cells. Ultimately loss of zinc finger protein expression detected is a promising and valuable biomarker for cancer aggressiveness and metastasis in the personalized care of prostate cancer. * DATA is unpublished