Abstract:
:Canonical Wnt signaling is altered in most cases of colorectal cancer. Experimental evidence indicates that protein phosphatase 2A (PP2A) may play either positive or negative roles in Wnt signaling but its precise in vivo functions remain elusive. In this work, using colon cultured cell lines we showed that basal PP2A activity is markedly reduced in malignant cells compared to non-malignant counterparts. We found that whereas normal or cancer cells displaying not altered Wnt signaling express mRNAs coding for PP2A-A scaffold α and β isoforms, cancer cells which have altered Wnt signaling do not express the Aβ isoform mRNA. Remarkably, we found that the Aβ protein levels are lost in all colon cancer cells, and in patients' tumor biopsies. In addition, all cancer cells exhibit higher levels of RalA activity, compared to non-malignant cells. Rescue experiments to restore Aβ expression in malignant RKO cells, diminished the RalGTPase activation and cell proliferation, indicating that the Aβ isoform acts as tumor suppressor in colon cancer cells. Reciprocal co-immunoprecipitation and immunofluorescence studies showed that the PP2A-C and -Aα subunits, expressed in all colon cells, interact in vivo with β-catenin only in malignant cells. Selective inhibition of PP2A did not significantly affect cellular apoptosis but induced dose-dependent negative effects in β-catenin-mediated transcriptional activity and in cell proliferation of malignant cells, indicating that the residual PP2A activity found in malignant cells, mediated by -C and Aα core subunits, is essential to maintain active Wnt signaling and cell proliferation in colon cancer cells.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Carmen Figueroa-Aldariz M,Castañeda-Patlán MC,Santoyo-Ramos P,Zentella A,Robles-Flores Mdoi
10.1002/mc.22217subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1430-41issue
11eissn
0899-1987issn
1098-2744journal_volume
54pub_type
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940140209
更新日期:1995-10-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20720
更新日期:2011-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2009-07-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22458
更新日期:2016-12-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23151
更新日期:2020-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22196
更新日期:2015-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050412
更新日期:1992-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940030506
更新日期:1990-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23013
更新日期:2019-07-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2009-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22099
更新日期:2015-04-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199606)16:2<83::AID-MC4>3.
更新日期:1996-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
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更新日期:2013-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050311
更新日期:1992-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22272
更新日期:2016-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20310
更新日期:2007-10-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940080404
更新日期:1993-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22033
更新日期:2014-10-01 00:00:00
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journal_title:Molecular carcinogenesis
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更新日期:2016-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1999-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2005-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1999-04-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22580
更新日期:2017-03-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20143
更新日期:2006-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
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journal_title:Molecular carcinogenesis
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doi:10.1002/mc.21852
更新日期:2013-04-01 00:00:00
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更新日期:1989-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/mc.23010
更新日期:2019-07-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010108
更新日期:1988-01-01 00:00:00