In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 18 ( 2003-09-02), p. 10429-10434
Abstract:
E-cadherin loss in cancer is associated with de-differentiation, invasion,
and metastasis. Drosophila DE-cadherin is regulated by
Wnt/β-catenin signaling, although this has not been demonstrated in mammalian cells. We previously reported that expression of WNT7a, encoded on
3p25, was frequently downregulated in lung cancer, and that loss of E-cadherin or β-catenin was a poor prognostic feature. Here we show that WNT7a both
activates E-cadherin expression via a β-catenin specific mechanism in lung cancer cells and is involved in a positive feedback loop. Li + ,
a GSK3β inhibitor, led to E-cadherin induction in an inositol-independent manner. Similarly, exposure to mWNT7a specifically induced free β-catenin
and E-cadherin. Among known transcriptional suppressors of E-cadherin, ZEB1 was uniquely correlated with E-cadherin loss in lung cancer cell lines, and
its inhibition by RNA interference resulted in E-cadherin induction. Pharmacologic reversal of E-cadherin and WNT7a losses was achieved with
Li + , histone deacetylase inhibition, or in some cases only with
combined inhibitors. Our findings provide support that E-cadherin induction by WNT/β-catenin signaling is an evolutionarily conserved pathway operative
in lung cancer cells, and that loss of WNT7a expression may be important in lung cancer development or progression by its effects on E-cadherin.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1734137100
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2003
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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