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Cited by 112Cytokine Signaling Pathways and InteractionsProtein Tyrosine PhosphatasesTGF-β signaling in diseases

Malignant Transformation but not Normal Cell Growth Depends on Signal Transducer and Activator of Transcription 3

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Schlessinger, Karni, Levy, David E.·2005·Cancer Research
DOI 10.1158/0008-5472.can-05-0317PMC PMC2100417

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Abstract

Signal transducer and activator of transcription 3 (STAT3) has been indirectly implicated in numerous fundamental cellular processes, including proliferation, survival, and differentiation. We provide genetic evidence from studies of STAT3-null cells that STAT3 is dispensable for normal growth of mouse fibroblasts in culture. STAT3 contributed to the full induction of some (typified by c-fos) but not all (typified by c-myc) immediate early gene expression, but STAT3-independent processes were sufficient to support full cell growth and survival. However, STAT3 was required to manifest a transformed state following expression of v-src, and STAT3-null cells were impaired for anchorage-independent growth as colonies in soft agar and as tumors in mice. The data suggest that STAT3 mediates the maintenance of focal adhesion kinase activity in the absence of cell adhesion by suppressing the action of an inhibitory phosphatase.

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  • STAT3 is a critical driver of cell growth in cancer, but not in normal cells.

    “STAT3 is a critical driver of cell growth in cancer, but not in normal cells.68”

    From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [68]

    The Abstract reports that STAT3-null mouse fibroblasts grew normally, while STAT3 was required for v-src transformation and growth in soft agar and as tumors in mice. The Discussion describes this as a transformation-specific function. The claim extends those findings to cancer cells and normal cells generally, beyond the fibroblast models studied; page numbers are not available in the supplied copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Schlessinger, K., & Levy, D. E.
Affiliations
New York University (US)
ORCID
Levy, David E.
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2005-07-01
Volume
65
Issue
13
Pages
5828-5834
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-05-0317
PMC
PMC2100417
OpenAlex
W2033860910
Cited by
112
References
2
Citations by year
2025: 2 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 2 · 2013: 9 · 2012: 5
FWCI
3.11
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI 28900, R01AI028900)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
STAT3, malignant transformation, fibroblast proliferation, cell survival, c-fos, c-Myc, immediate early gene expression, v-Src, anchorage-independent growth, tumor formation, focal adhesion kinase, cell adhesion
MeSH terms
Animals, Cell Adhesion, Cell Transformation, Neoplastic, Cells, Cultured, DNA-Binding Proteins, Enzyme Activation, Fibroblasts, Gene Expression Regulation, Mice, Inbred BALB C, Protein-Tyrosine Kinases, Trans-Activators, Oncogene Protein pp60(v-src), Genes, src, Proto-Oncogene Proteins c-fos, Genes, fos, Cell Growth Processes, STAT3 Transcription Factor, Mice, Focal Adhesion Protein-Tyrosine Kinases, Focal Adhesion Kinase 1

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