The zinc finger transcription factor ZKSCAN3 promotes prostate cancer cell migration

Abstract

In our previous studies, ZKSCAN3 was demonstrated to be over-expressed in invasive colonic tumor cells and their liver metastases, but minimally expressed in adjacent non-transformed tissues. Further preliminary data showed that ZKSCAN3 was expressed in a majority of prostate cancer patient samples, but not in normal prostate tissues. Moreover, the ZKSCAN3 protein is highly expressed in the PC3 prostate cancer cell line, which has high metastatic potential, but little expression was observed in non-metastatic prostate cancer cell lines. Thus, we hypothesized that ZKSCAN3 could participate in tumor metastasis by regulating tumor cell migration. To test this hypothesis, ZKSCAN3 mRNA was knocked down by ZKSCAN3 specific shRNA in PC3 cells and a significant decrease in cell motility was observed. In contrast, when ZKSCAN3 cDNA was overexpressed in PC3 cells, cell detachment was observed and suspension culture induced apoptosis was greatly decreased, suggesting that ZKSCAN3 is able to enhance PC3 cell survival under anoikis stress. Additional wound healing and invasion assays showed that cell migration was enhanced by ZKSCAN3 expression. Interestingly, the ZKSCAN3 gene was amplified in 26% (5/19) of metastatic prostate cancers and 20% (1/5) of lymph node metastases, but there was no amplification found in primary prostate cancers, further supporting the role of ZKSCAN3 in tumor cell migration. In vivo studies using orthotopic tumor models indicated that overexpression of ZKSCAN3 significantly enhanced tumorigenicity. Taken together, we provide evidence that ZKSCAN3, a zinc finger transcription factor, plays a critical role in promoting prostate cancer cell migration.

ZNF667 Serves as a Putative Oncogene in Human Hepatocellular Carcinoma

“…The researchers found that down-regulation of ZKSCAN3 significantly inhibited tumor growth in colon cancer cells, whereas overexpression of ZKSCAN3 produced the opposite effect. In addition, ZKSCAN3 was found to be highly expressed in multiple myeloma [23, 24] and prostate cancer [25]. Through transcriptional activation of cyclin D2 expression, ZKSCAN3 enhanced tumor cell proliferation.…”

Recurrent patterns of DNA methylation in theZNF154,CASP8, andVHLpromoters across a wide spectrum of human solid epithelial tumors and cancer cell lines

“…Certain proteins encoding specific zincfinger domains have been reported to recognize non-methylated DNA and to recruit chromatin-modifying elements to CpG islands, 50 and there is evidence for the implication of several zincfinger transcription factors in cancer. [51][52][53][54][55] Hypermethylation of ZNF154 has previously been reported by independent sources to occur in bladder, 18,56 breast, 57 head and neck, 58,59 hepatocellular, 60 lung, 29 ovarian, 25,61 prostate, 62 and renal 63 cancers. Still, very little is known about the biological function of the protein encoded by ZNF154, and the possible functional significance Figure 3.…”

ZKSCAN3 expression in urothelial carcinoma of the upper urinary tract and its impact on patient outcomes

“…ZKSCAN3, a family member of the KRAB and SCAN domaincontaining zinc-finger transcription factors, has been shown to involve the outgrowth of malignancies [3][4][5][6]. It has indeed been documented that overexpression or gene amplification of ZKSCAN3 in tissue specimens correlates with colorectal cancer invasion [4] or prostate cancer metastasis [4], respectively.…”

“…It has indeed been documented that overexpression or gene amplification of ZKSCAN3 in tissue specimens correlates with colorectal cancer invasion [4] or prostate cancer metastasis [4], respectively. Recently, we demonstrated that ZKSCAN3 knockdown in bladder cancer lines resulted in considerable decreases in cell viability, along with increased apoptosis, as well as in cell migration and invasion [6].…”