WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors

  • Authors:
    • G. Pannone
    • P. Bufo
    • A. Santoro
    • R. Franco
    • G. Aquino
    • F. Longo
    • G. Botti
    • R. Serpico
    • B. Cafarelli
    • A. Abbruzzese
    • M. Caraglia
    • S. Papagerakis
    • L. Lo Muzio
  • View Affiliations

  • Published online on: October 1, 2010     https://doi.org/10.3892/or_00000952
  • Pages: 1035-1041
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Abstract

Epigenetic DNA methylations plays an important role in oral carcinogenesis. The soluble frizzled receptor protein (SFRP) family together with WIF-1 and DKK-3 encodes antagonists of the WNT pathway. Silencing of these genes leads to constitutive WNT signalling. Because aberrant expression of β-catenin might be associated with the epigenetic inactivation of WNT inhibitors, we analyzed, in a collection of primary OSCC with matched normal oral mucosa, the methylation status of a complete panel of genes, SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3, that are involved directly and indirectly in WNT pathway, in order to demonstrate WNT-pathway activation in the absence of β-catenin and/or APC/Axin mutations during oral carcinogenesis. Methylation-specific PCR (MSP) was performed to study inactivation of SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 genes in 37 cases of paraffin embedded oral cancer. This study showed that the methylation is an important epigenetic alteration in oral cancer. In particular, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 revealed methylation status of their promoter in OSCC, whereas SFRP-1 showed demethylation in cancer. Fisher's exact test revealed statistically significant results (p<0.05) for all genes. The Wald test confirmed the statistically significant association between SFRP2-4-5 gene methylation and OSCC (p<0.05). SFRP-1 was also characterized by a different statistically significant epigenetic behaviour, because of it was demethylated in cancer (p<0.05). Statistical regression test showed high levels of sensitivity, specificity and accuracy for SFRP genes, while WIF-1 and DKK-3 have reportedly high specificity, moderate accuracy but low sensitivity. This study suggests that a cause of catenin delocalization in oral cancer could be due to WNT pathway activation, by epigenetic alterations of SFRP, WIF-1 and DKK-3 genes.

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October 2010
Volume 24 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Pannone G, Bufo P, Santoro A, Franco R, Aquino G, Longo F, Botti G, Serpico R, Cafarelli B, Abbruzzese A, Abbruzzese A, et al: WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors . Oncol Rep 24: 1035-1041, 2010.
APA
Pannone, G., Bufo, P., Santoro, A., Franco, R., Aquino, G., Longo, F. ... Lo Muzio, L. (2010). WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors . Oncology Reports, 24, 1035-1041. https://doi.org/10.3892/or_00000952
MLA
Pannone, G., Bufo, P., Santoro, A., Franco, R., Aquino, G., Longo, F., Botti, G., Serpico, R., Cafarelli, B., Abbruzzese, A., Caraglia, M., Papagerakis, S., Lo Muzio, L."WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors ". Oncology Reports 24.4 (2010): 1035-1041.
Chicago
Pannone, G., Bufo, P., Santoro, A., Franco, R., Aquino, G., Longo, F., Botti, G., Serpico, R., Cafarelli, B., Abbruzzese, A., Caraglia, M., Papagerakis, S., Lo Muzio, L."WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors ". Oncology Reports 24, no. 4 (2010): 1035-1041. https://doi.org/10.3892/or_00000952