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WNT5a‐mediated tumor suppression of esophageal adenocarcinoma in vitro
Author(s) -
Moore Tami,
Lyros Orestis,
Nie Linghui,
Jovanovic Nebojsa,
Medda Rituparna,
Perkins Tiffani,
Otterson Mary,
Shaker Reza
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1087.17
Subject(s) - wnt signaling pathway , axin2 , cyclin d1 , wnt5a , cancer research , carcinogenesis , immunohistochemistry , adenocarcinoma , beta catenin , biology , esophagus , medicine , cancer , signal transduction , cell cycle , microbiology and biotechnology
Background The incidence of esophageal adenocarcinoma (EAC) has increased over the last decade while its prognosis still remains poor. Barrett's esophagus (BE) is the only known precursor of EAC while the underlying molecular mechanisms are unknown. Wnt5a is a member of the non‐transforming WNT family whose role in carcinogenesis is still ambiguous. Wnt5a functions through ROR2 receptor and exhibits tumor suppression in colorectal cancer. We investigated the role of Wnt5a in esophageal adenocarcinoma. Methods Gene and protein expression of Wnt5a and ROR2 were analyzed in human esophageal tissues (healthy, BE, and EAC) and various esophageal cell lines by qRT‐PCR and immunohistochemistry respectively. Cell proliferation, survival and migration were assessed in OE33 cancer cells following rWnt5a treatment. Western blotting determined GSK3 β‐phosphorylation. Nuclear β‐catenin localization and Axin2 & Cyclin D1 gene expression were also determined. Results Wnt5a was down‐regulated or sustained whereas ROR2 was overexpressed in BE and EAC tissues compared to healthy controls. Same findings were confirmed in vitro . rWnt5a inhibited cell proliferation, survival, and migration in OE33 cells in a dose‐dependent manner. rWnt5a inhibited GSK3β phosphorylation but did not alter β‐catenin activity. Conclusions Wnt5a mediates tumor suppression in OE33 cells. ROR2 receptor may mediate this effect.