Roles of activated Src and Stat3 signaling in melanoma tumor cell growth
Abstract
Activation of protein tyrosine kinases is prevalent in human cancers and previous studies have demonstrated that Stat3 signaling is a point of convergence for many of these tyrosine kinases. Moreover, a critical role for constitutive activation of Stat3 in tumor cell proliferation and survival has been established in diverse cancers. However, the oncogenic signaling pathways in melanoma cells remain to be fully defined. In this study, we demonstrate that Stat3 is constitutively activated in a majority of human melanoma cell lines and tumor specimens examined. Blocking Src tyrosine kinase activity, but not EGF receptor or JAK family kinases, leads to inhibition of Stat3 signaling in melanoma cell lines. Consistent with a role of Src in the pathogenesis of melanoma, we show that c-Src tyrosine kinase is activated in melanoma cell lines. Significantly, melanoma cells undergo apoptosis when either Src kinase activity or Stat3 signaling is inhibited. Blockade of Src or Stat3 is also accompanied by down-regulation of expression of the anti-apoptotic genes, Bcl-x(L) and Mcl-1. These findings demonstrate that Src-activated Stat3 signaling is important for the growth and survival of melanoma tumor cells.
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Constitutive STAT3 signaling has been implicated in aberrant cell growth and proliferation in many cancers, including head and neck squamous cell carcinoma, colorectal carcinoma, melanoma, glioblastoma multiforme, multiple myeloma, non-small cell lung cancer, and others.
“Constitutive STAT3 signaling has been implicated in aberrant cell growth and proliferation in many cancers, including head and neck squamous cell carcinoma, colorectal carcinoma, melanoma, glioblastoma multiforme, multiple myeloma, non-small cell lung cancer, and others.58,69–73”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [70]
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- Authors
- Niu, G., Bowman, T., Huang, M., Shivers, S., Reintgen, D., Daud, A., Chang, A., Kraker, A., Jove, R., & Yu, H.
- Affiliations
- University of South Florida (US)
- University of Michigan (US)
- Pfizer (United States) (US)
- Venue
- Oncogene
- Published
- 2002-10-09
- Volume
- 21
- Issue
- 46
- Pages
- 7001-7010
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1996112634
- Cited by
- 432
- References
- 3
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 13 · 2022: 13 · 2021: 18 · 2020: 17 · 2019: 19 · 2018: 10 · 2017: 21 · 2016: 17 · 2015: 17 · 2014: 19 · 2013: 23 · 2012: 27
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA75243, R01CA055652, CA 82533, CA89693, CA-55652, R01CA089693, P01CA082533, R29CA075243)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- melanoma, Src kinase, STAT3 signaling, constitutive STAT3 activation, tumor cell proliferation, apoptosis, Bcl-xL, Mcl-1, anti-apoptotic genes, oncogenic signaling, tyrosine kinase
- MeSH terms
- Cell Division, DNA, DNA-Binding Proteins, Enzyme Activation, Humans, Melanoma, Neoplasm Proteins, Pyridones, Pyrimidines, Tumor Cells, Cultured, Trans-Activators, Apoptosis, src-Family Kinases, Proto-Oncogene Proteins c-bcl-2, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, STAT3 Transcription Factor, bcl-X Protein, Myeloid Cell Leukemia Sequence 1 Protein, ErbB Receptors
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