The XXXX suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal @entity189 .

@entity5 @entity189 @entity876 @entity3546 @entity11408 @entity21124 @entity11508
Aberrant activation of the wingless-type- (Wnt)-signaling pathway is common in many @entity5 including nasopharyngeal ( @entity11408 ) and esophageal squamous cell (ESCC) @entity189 , both prevalent in Southern China and Southeast Asia. However, the molecular mechanism leading to this abnormality is still obscure. @entity21124 ( @entity21124 ) is a secreted antagonist of the Wnt pathway, and is recently shown to be inactivated by epigenetic mechanism in some @entity5 . Here, we examined whether @entity21124 is also inactivated epigenetically in @entity11408 and ESCC. With semiquantitative reverse transcription-PCR and methylation-specific PCR, we detected @entity21124 downregulation or silencing in 6/6 of @entity11408 and 12/19 of ESCC cell lines, which is well correlated with its methylation status. Methylation was further confirmed by high-resolution bisulfite genomic sequencing. Methylation was also frequently observed in a large collection of @entity5 of @entity11408 (85%, 55/65) and ESCC (27%, 25/92), with @entity21124 expressed and unmethylated in normal @entity11408 and esophageal cell lines and normal tissues. Treatment of @entity11508 demethylated @entity21124 and induced its expression in @entity11408 and ESCC cell lines, highlighting a direct role of epigenetic inactivation. Ectopic expression of @entity21124 in @entity11408 and @entity5 cells resulted in significant @entity5 cell colony formation, similar to @entity876 , and also significant downregulation of @entity3546 protein level in @entity11408 cells. Thus, @entity21124 functions as a @entity5 suppressor for both @entity11408 and ESCC through suppressing the Wnt-signaling pathway, but is frequently silenced by epigenetic mechanism in a @entity5 -specific way. Our study indicates that epigenetic inactivation of @entity21124 contributes to the aberrant activation of Wnt pathway and is involved in the pathogenesis of both @entity5 . @entity21124 methylation could also serve as a specific biomarker for these @entity5 .
