WNT5A antagonizes WNT/β-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinoma

Jisheng Li, Jianming Ying, Yichao Fan, Longtao Wu, Ying Ying, Anthony Tak-cheung Chan, Gopesh Srivastava, Qian Tao

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

WNT5A is classified as a non-transforming WNT family member whose role in carcinogenesis is still ambiguous. It exhibits tumor suppressor activities in some cancers (thyroid, brain, breast and colorectum), but is aberrantly upregulated in cancers of lung, stomach and prostate. We investigated its epigenetic alterations and functions in esophageal squamous cell carcinoma (ESCC). With semi-quantitative reverse transcription PCR, we found that WNT5A was silenced or downregulated in 5 of 18 ESCC cell lines, but expressed in normal esophagus tissue and immortalized normal esophageal epithelial cell lines. promoter cpG methylation of WNT5A was detected in 4 of the 5 downregulated ESCC cell lines, while 5-aza-2′-deoxycytidine treatment induced WNT5A expression and demethylated its promoter in silenced cell lines. WNT5A promoter methylation was frequently detected in primary ESCC (24/36, 67%), but less frequently and weakly in paired surgical marginal esophageal tissues (8/36, 22%; p < 0.01), while no methylation was detected in seven normal esophageal epithelial tissues from healthy donors. ectopic expression of WNT5A resulted in significant inhibition of clonogenicity and motility of ESCC cells, accompanied by a dramatic decrease of intracellular β-catenin protein level and β-catenin transcriptional activity. In summary, we show that WNT5A is frequently silenced in ESCC by promoter methylation and exhibits tumor suppressor properties through antagonizing the WNT/β-catenin pathway. The epigenetic disruption of WNT5A would thus contribute directly to the aberrant activation of WNT/β-catenin signaling during ESCC pathogenesis.

Original languageEnglish (US)
Pages (from-to)617-624
Number of pages8
JournalCancer Biology and Therapy
Volume10
Issue number6
DOIs
StatePublished - Sep 15 2010

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Catenins
Methylation
Cell Line
decitabine
Epigenomics
Down-Regulation
Esophageal Squamous Cell Carcinoma
Thyroid Neoplasms
Brain Neoplasms
Esophagus
Reverse Transcription
Stomach Neoplasms
Lung Neoplasms
Neoplasms
Prostatic Neoplasms
Carcinogenesis
Breast
Epithelium
Epithelial Cells
Tissue Donors

Keywords

  • Esophageal squamous cell carcinoma
  • Methylation
  • Tumor suppressor gene
  • WNT signaling
  • WNT5A

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

WNT5A antagonizes WNT/β-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinoma. / Li, Jisheng; Ying, Jianming; Fan, Yichao; Wu, Longtao; Ying, Ying; Chan, Anthony Tak-cheung; Srivastava, Gopesh; Tao, Qian.

In: Cancer Biology and Therapy, Vol. 10, No. 6, 15.09.2010, p. 617-624.

Research output: Contribution to journalArticle

Li, Jisheng ; Ying, Jianming ; Fan, Yichao ; Wu, Longtao ; Ying, Ying ; Chan, Anthony Tak-cheung ; Srivastava, Gopesh ; Tao, Qian. / WNT5A antagonizes WNT/β-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinoma. In: Cancer Biology and Therapy. 2010 ; Vol. 10, No. 6. pp. 617-624.
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