Alternative titles; symbols
HGNC Approved Gene Symbol: ZKSCAN3
Cytogenetic location: 6p22.1 Genomic coordinates (GRCh38): 6:28,349,878-28,369,172 (from NCBI)
By screening a human colon cancer cell line expression library for regulators of UPAR (PLAUR; 173391) promoter activity, Wang et al. (2004) cloned ZKSCAN3, which they called ZNF306. The deduced 538-amino acid protein belongs to the Kruppel-like subfamily of C2H2 zinc finger proteins and shares significant similarity with KLF4 (602253).
By searching EST databases for genes upregulated in colorectal cancers, Yang et al. (2008) identified ZKSCAN3. The deduced protein contains 2 tandem C2H2 zinc finger domains. Immunohistochemical analysis showed that ZKSCAN3 localized to tumor cell nuclei.
Yang et al. (2008) showed that expression of ZKSCAN3 was upregulated in primary colorectal tumors compared with adjacent nonmalignant mucosa. Expression of ZKSCAN3 was higher in invasive tumors compared with noninvasive tumors. Southern blot analysis revealed that overexpression in some tumors was partly due to gene amplification. Knockdown of ZKSCAN3 in 2 independent colon cancer cell lines impaired anchorage-independent growth and tumor growth in nude mice, whereas overexpression in a third cell line had the opposite effect. Small interfering RNA targeting ZKSCAN3 reduced tumorigenicity of colon cancer cells in nude mice.
Yang et al. (2008) determined that ZKSCAN3 bound the consensus DNA sequence (G/T)(A/G)(A/G/T)GGGG. Expression profiling showed that 204 genes were induced 2- to 29-fold and 76 genes were reduced 2- to 5-fold by ZKSCAN3 in transfected human colon cancer cells compared with parental cells. Of the genes upregulated by ZKSCAN3, the majority encoded proteins involved in growth, cell migration, angiogenesis, and proteolysis. Yang et al. (2008) confirmed that ZKSCAN3 bound the promoter of integrin beta-4 (ITGB4; 147557), a gene upregulated 6-fold by ZKSCAN3, in vitro and in vivo. ITGB4 knockdown by short hairpin RNA countered ZKSCAN3-augmented anchorage-independent colony formation in the colon cancer cell lines. Yang et al. (2008) also confirmed that VEGF (192240) was a direct target of ZKSCAN3. They concluded that ZKSCAN3 regulates expression of genes favoring tumor progression.
By genomic sequence analysis, Yang et al. (2008) mapped the ZKSCAN3 gene to chromosome 6p22.1.
Wang, H., Yang, L., Jamaluddin, M. S., Boyd, D. D. The Kruppel-like KLF4 transcription factor, a novel regulator of urokinase receptor expression, drives synthesis of this binding site in colonic crypt luminal surface epithelial cells. J. Biol. Chem. 279: 22674-22683, 2004. [PubMed: 15031282] [Full Text: https://doi.org/10.1074/jbc.M401257200]
Yang, L., Hamilton, S. R., Sood, A., Kuwai, T., Ellis, L., Sanguino, A., Lopez-Berestein, G., Boyd, D. D. The previously undescribed ZKSCAN3 (ZNF306) is a novel 'driver' of colorectal cancer progression. Cancer Res. 68: 4321-4330, 2008. [PubMed: 18519692] [Full Text: https://doi.org/10.1158/0008-5472.CAN-08-0407]
Yang, L., Zhang, L., Wu, Q., Boyd, D. D. Unbiased screening for transcriptional targets of ZKSCAN3 identifies integrin beta-4 and vascular endothelial growth factor as downstream targets. J. Biol. Chem. 283: 35295-35304, 2008. [PubMed: 18940803] [Full Text: https://doi.org/10.1074/jbc.M806965200]