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DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3.
Oncogene. 2008 Jul 24; 27(32):4467-77.O

Abstract

Aberrant activation of the Wnt/beta-catenin signaling pathway is a hallmark of colon cancer. We show that the Wnt antagonist DICKKOPF-4 (DKK-4) gene is repressed by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in human colon cancer cells. This effect correlated with the inhibition of the DKK-4 promoter. Chromatin immunoprecipitation assays revealed that 1,25(OH)2D3 induces early and transient binding of the vitamin D receptor (VDR) and the SMRT corepressor to the region adjacent to the transcription start site of DKK-4. Additionally, we demonstrate that the DKK-4 gene is a new downstream target of TCF/beta-catenin. Remarkably, expression of DKK-4 messenger RNA (mRNA) was not detected in a series of 29 human normal (N) colon biopsies but expression was upregulated in all the matched tumour (T) tissues. An inverse correlation existed between the expression of DKK-4 and VDR RNA in the Ts. Ectopic DKK-4 expression increased the migration and invasion properties of colon cancer cells and conditioned media (CM) from DKK-4-expressing cells enhanced the capacity to migrate and form capillary-like tubules of human primary microvascular endothelial cells. In conclusion, DKK-4 is upregulated in colon cancer and is associated with the acquisition of malignant properties by neoplastic cells. DKK-4 downregulation is a novel effect of 1,25(OH)2D3 that may contribute to its anticancer action.

Authors+Show Affiliations

Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18408752

Citation

Pendás-Franco, N, et al. "DICKKOPF-4 Is Induced By TCF/beta-catenin and Upregulated in Human Colon Cancer, Promotes Tumour Cell Invasion and Angiogenesis and Is Repressed By 1alpha,25-dihydroxyvitamin D3." Oncogene, vol. 27, no. 32, 2008, pp. 4467-77.
Pendás-Franco N, García JM, Peña C, et al. DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3. Oncogene. 2008;27(32):4467-77.
Pendás-Franco, N., García, J. M., Peña, C., Valle, N., Pálmer, H. G., Heinäniemi, M., Carlberg, C., Jiménez, B., Bonilla, F., Muñoz, A., & González-Sancho, J. M. (2008). DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3. Oncogene, 27(32), 4467-77. https://doi.org/10.1038/onc.2008.88
Pendás-Franco N, et al. DICKKOPF-4 Is Induced By TCF/beta-catenin and Upregulated in Human Colon Cancer, Promotes Tumour Cell Invasion and Angiogenesis and Is Repressed By 1alpha,25-dihydroxyvitamin D3. Oncogene. 2008 Jul 24;27(32):4467-77. PubMed PMID: 18408752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3. AU - Pendás-Franco,N, AU - García,J M, AU - Peña,C, AU - Valle,N, AU - Pálmer,H G, AU - Heinäniemi,M, AU - Carlberg,C, AU - Jiménez,B, AU - Bonilla,F, AU - Muñoz,A, AU - González-Sancho,J M, Y1 - 2008/04/14/ PY - 2008/4/15/pubmed PY - 2008/8/22/medline PY - 2008/4/15/entrez SP - 4467 EP - 77 JF - Oncogene JO - Oncogene VL - 27 IS - 32 N2 - Aberrant activation of the Wnt/beta-catenin signaling pathway is a hallmark of colon cancer. We show that the Wnt antagonist DICKKOPF-4 (DKK-4) gene is repressed by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in human colon cancer cells. This effect correlated with the inhibition of the DKK-4 promoter. Chromatin immunoprecipitation assays revealed that 1,25(OH)2D3 induces early and transient binding of the vitamin D receptor (VDR) and the SMRT corepressor to the region adjacent to the transcription start site of DKK-4. Additionally, we demonstrate that the DKK-4 gene is a new downstream target of TCF/beta-catenin. Remarkably, expression of DKK-4 messenger RNA (mRNA) was not detected in a series of 29 human normal (N) colon biopsies but expression was upregulated in all the matched tumour (T) tissues. An inverse correlation existed between the expression of DKK-4 and VDR RNA in the Ts. Ectopic DKK-4 expression increased the migration and invasion properties of colon cancer cells and conditioned media (CM) from DKK-4-expressing cells enhanced the capacity to migrate and form capillary-like tubules of human primary microvascular endothelial cells. In conclusion, DKK-4 is upregulated in colon cancer and is associated with the acquisition of malignant properties by neoplastic cells. DKK-4 downregulation is a novel effect of 1,25(OH)2D3 that may contribute to its anticancer action. SN - 1476-5594 UR - https://www.unboundmedicine.com/medline/citation/18408752/DICKKOPF_4_is_induced_by_TCF/beta_catenin_and_upregulated_in_human_colon_cancer_promotes_tumour_cell_invasion_and_angiogenesis_and_is_repressed_by_1alpha25_dihydroxyvitamin_D3_ L2 - https://doi.org/10.1038/onc.2008.88 DB - PRIME DP - Unbound Medicine ER -