Cited by 325Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingSignaling Pathways in Disease

The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.

Identification of specific PP2A complexes involved in human cell transformation

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Abstract

The SV40 small t antigen (ST) interacts with the serine-threonine protein phosphatase 2A (PP2A). To investigate the role of this interaction in transformation, we suppressed the expression of the PP2A B56gamma subunit in human embryonic kidney (HEK) epithelial cells expressing SV40 large T antigen, hTERT, and H-RAS. Suppression of PP2A B56gamma expression inhibited PP2A-specific phosphatase activity similar to that achieved by ST and conferred the ability to grow in an anchorage-independent fashion and to form tumors. Overexpression of PP2A B56gamma3 in tumorigenic HEK cells expressing ST or human lung cancer cell lines partially reversed the tumorigenicity of these cells. These observations identify specific PP2A complexes involved in human cell transformation.

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Crossref · 10.1016/s1535-6108(04)00026-1

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56 of 56 references verified0 citation errors · 0 not checkable

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  • PP2A trimers with B56 subunits are predominantly human tumour suppressors.

    “Among the PP2A complexes, PP2A trimers with B56 subunits are predominantly human tumour suppressors4–7.”
  • CIP2A K21A targeted clones were almost completely incompetent to grow as spheres on soft agar.

    “However, fully consistent with the requirement of PP2A-B56 inhibition for anchorage-independent growth6,7, CIP2A K21A targeted clones were almost completely incompetent to grow as spheres on soft agar (Fig. 3F, G).”
  • PP2A-B56α is a human tumour suppressor.

    “The protein phosphatase 2A (PP2A) heterotrimer PP2A-B56α is a human tumour suppressor.”
  • Ectopic B56γ expression in lung, breast and prostate cancer cell lines reduces proliferation and colony formation in soft agar.

    “Consistently, ectopic expression of B56γ in lung, breast and prostate cancer cell lines reduced cell proliferation and colony formation in soft agar, suggesting a potential tumor suppressor role of B56γ in multiple cell types (Chen et al., 2004).”
  • The role of B′ subunits as tumor suppressors is corroborated by the notion that B′ subunit knockdown causes polyploidy.

    “This notion corroborates with the previous notion on the role of B′ subunits as tumor suppressors [45–49].”

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Metadata

Authors
Chen, W., Possemato, R., Campbell, K. T., Plattner, C. A., Pallas, D. C., & Hahn, W. C.
Affiliations
  • Brigham and Women's Hospital (US)
  • Emory University (US)
Corresponding author
Hahn, William C
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2004-02
Volume
5
Issue
2
Pages
127-136
ISSN
1535-6108 (ISSN-L)
OpenAlex
W1971212979
Cited by
325
References
56
Citations by year
2026: 1 · 2025: 6 · 2024: 2 · 2023: 14 · 2022: 10 · 2021: 12 · 2020: 14 · 2019: 16 · 2018: 13 · 2017: 9 · 2016: 8 · 2015: 13 · 2014: 15 · 2013: 14 · 2012: 19
FWCI
9.95
Type
journal article
Language
en
Update notices
erratum (2024-06-10)
Open access
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (R01 CA57327, P01 CA 50661, K01CA94223, K01CA094223, P01CA050661, R01CA057327)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
protein phosphatase 2A, small T antigen, SV40 large T antigen, cell transformation, anchorage-independent growth, tumorigenicity, H-Ras, hTERT, lung cancer
MeSH terms
Animals, Antigens, Viral, Tumor, Cell Transformation, Neoplastic, Cells, Cultured, Cloning, Molecular, DNA-Binding Proteins, Enzyme Activation, Epithelial Cells, Humans, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Genes, ras, Signal Transduction, Telomerase, Protein Subunits, Protein Phosphatase 2

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