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Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis
Open accessAbstract
Signal transducer and activator of transcription (STAT) proteins perform key roles in mediating signaling by cytokines and growth factors, including platelet-derived growth factor (PDGF). In addition, Src family kinases activate STAT signaling and are required for PDGF-induced mitogenesis in normal cells. One STAT family member, Stat3, has been shown to have an essential role in cell transformation by the Src oncoprotein. However, the mechanisms by which STAT-signaling pathways contribute to mitogenesis and transformation are not fully defined. We show here that disruption of Stat3 signaling by using dominant-negative Stat3β protein in NIH 3T3 fibroblasts suppresses c-Myc expression concomitant with inhibition of v-Src-induced transformation. Ectopic expression of c-Myc is able to partially reverse this inhibition, suggesting that c-Myc is a downstream effector of Stat3 signaling in v-Src transformation. Furthermore, c -myc gene knockout fibroblasts are refractory to transformation by v-Src, consistent with a requirement for c-Myc protein in v-Src transformation. In normal NIH 3T3 cells, disruption of Stat3 signaling with dominant-negative Stat3β protein inhibits PDGF-induced mitogenesis in a manner that is reversed by ectopic c-Myc expression. Moreover, inhibition of Src family kinases with the pharmacologic agent, SU6656, blocks Stat3 activation by PDGF. These findings, combined together, delineate the signaling pathway, PDGF → Src → Stat3 → Myc, that is important in normal PDGF-induced mitogenesis and subverted in Src transformation.
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“In addition, the STAT3 target gene MYC, which itself encodes a transcription factor, is also a potent promoter of cell growth and is required for Src-mediated cellular transformation via STAT3.45”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [45]
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Cites
Darnell, J. E. (1997) · Science · doi:10.1126/science.277.5332.1630 · Cited by 3,979
HOW CELLS RESPOND TO INTERFERONS
Stark, G. R., Kerr, I. M., Williams, B. R. G., Silverman, R. H., & Schreiber, R. D. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.227 · Cited by 3,932
Bromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C., & Darnell, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81959-5 · Cited by 2,790
Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor
Kelly, K., Cochran, B., Stiles, C. D., & Leder, P. (1983) · Cell · doi:10.1016/0092-8674(83)90092-2 · Cited by 2,227
Hunter, T. R., & Cooper, J. A. (1985) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.54.070185.004341 · Cited by 2,142
Bowman, T., Garcia, R., Turkson, J., & Jove, R. (2000) · Oncogene · doi:10.1038/sj.onc.1203527 · Cited by 1,743
Self-citationCatlett-Falcone, R., Landowski, T. H., Oshiro, M. M., Turkson, J., Levitzki, A., Savino, R., Ciliberto, G., Moscinski, L., Fernández-Luna, J. L., Nuñez, G., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80011-4 · Cited by 1,638
Self-citationMolecular themes in oncogenesis
Bishop, J. M. (1991) · Cell · doi:10.1016/0092-8674(91)90636-d · Cited by 1,629
The role of STATs in transcriptional control and their impact on cellular function
Bromberg, J., & Darnell, J. E. (2000) · Oncogene · doi:10.1038/sj.onc.1203476 · Cited by 1,201
Enhanced DNA-Binding Activity of a Stat3-Related Protein in Cells Transformed by the Src Oncoprotein
Yu, C.-L., Meyer, D. J., Campbell, G. S., Larner, A. C., Carter-Su, C., Schwartz, J., & Jove, R. (1995) · Science · doi:10.1126/science.7541555 · Cited by 931
Self-citationColler, H. A., Grandori, C., Tamayo, P., Colbert, T., Lander, E. S., Eisenman, R. N., & Golub, T. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3260 · Cited by 823
Fetal Anemia and Apoptosis of Red Cell Progenitors in Stat5a−/−5b−/− Mice
Socolovsky, M., Fallon, A. E. J., Wang, S., Brugnara, C., & Lodish, H. F. (1999) · Cell · doi:10.1016/s0092-8674(00)81013-2 · Cited by 695
Fukada, T., Hibi, M., Yamanaka, Y., Takahashi-Tezuka, M., Fujitani, Y., Yamaguchi, T., Nakajima, K., & Hirano, T. (1996) · Immunity · doi:10.1016/s1074-7613(00)80501-4 · Cited by 652
Stat3 Activation by Src Induces Specific Gene Regulation and Is Required for Cell Transformation
Turkson, J., Bowman, T., Garcia, R., Caldenhoven, E., De Groot, R. P., & Jove, R. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.5.2545 · Cited by 651
Self-citationStat3 Activation Is Required for Cellular Transformation by v- src
Bromberg, J. F., Horvath, C. M., Besser, D., Lathem, W. W., & Darnell, J. E. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.5.2553 · Cited by 614
The SIF binding element confers sis/PDGF inducibility onto the c‐fos promoter.
Wagner, B. J., Hayes, T. E., Hoban, C. J., & Cochran, B. H. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07898.x · Cited by 592
Grandis, J. R., Drenning, S. D., Zeng, Q., Watkins, S. C., Melhem, M. F., Endo, S., Johnson, D. E., Huang, L., He, Y., & Kim, J. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.8.4227 · Cited by 588
SU6656, a Selective Src Family Kinase Inhibitor, Used To Probe Growth Factor Signaling
Blake, R. A., Broome, M. A., Liu, X., Wu, J., Gishizky, M. L., Sun, L., & Courtneidge, S. A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.23.9018-9027.2000 · Cited by 580
Self-citationIdentification of CDK4 as a target of c-MYC
Hermeking, H., Rago, C., Schuhmacher, M., Li, Q., Barrett, J. F., Obaya, Á. J., O’Connell, B. C., Mateyak, M. K., Tam, W., Kohlhuber, F., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050586197 · Cited by 476
Self-citationPhenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.
Mateyak, M. K., Obaya, Á. J., Adachi, S., & Sedivy, J. M. (1997) · PubMed · Cited by 443
Self-citationSynergistic Roles for Pim-1 and c-Myc in STAT3-Mediated Cell Cycle Progression and Antiapoptosis
Shirogane, T., Fukada, T., Müller, J. M. M., Shima, D. T., Hibi, M., & Hirano, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80145-4 · Cited by 431
STAT3 Is Required for the gp130-mediated Full Activation of the c-myc Gene
Kiuchi, N., Nakajima, K., Ichiba, M., Fukada, T., Narimatsu, M., Mizuno, K., Hibi, M., & Hirano, T. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.1.63 · Cited by 401
Dominant negative MYC blocks transformation by ABL oncogenes
Sawyers, C. L., Callahan, W., & Witte, O. N. (1992) · Cell · doi:10.1016/0092-8674(92)90241-4 · Cited by 395
Function of the c-Myc Oncogenic Transcription Factor
Dang, C. V., Resar, L. M. S., Emison, E. S., Kim, S., Li, Q., Prescott, J. E., Wonsey, D. R., & Zeller, K. I. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4686 · Cited by 391
Caldenhoven, E., van Dijk, T. B., Solari, R., Armstrong, J., Raaijmakers, J. A. M., Lammers, J.-W. J., Koenderman, L., & de Groot, R. P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.22.13221 · Cited by 373
Garcia, R., Yu, C., Hudnall, A. M., Catlett, R., Nelson, K. L., Smithgall, T. E., Fujita, D. J., Ethier, S. P., & Jove, R. (1997) · PubMed · Cited by 369
Self-citationTwamley, G. M., Pepperkok, R., Ansorge, W., & Courtneidge, S. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.16.7696 · Cited by 333
Self-citationMateyak, M. K., Obaya, Á. J., & Sedivy, J. M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.7.4672 · Cited by 333
Self-citationJak-STAT Signaling Induced by the v- abl oncogene
Danial, N. N., Pernis, A., & Rothman, P. B. (1995) · Science · doi:10.1126/science.7569929 · Cited by 325
Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation.
Silvennoinen, O., Schindler, C., Schlessinger, J., & Levy, D. (1993) · Science · doi:10.1126/science.8378775 · Cited by 319
Niu, G., Heller, R. F., Catlett-Falcone, R., Coppola, D., Jaroszeski, M. J., Dalton, W. S., Jove, R., & Yu, H. (1999) · PubMed · Cited by 313
Self-citationMyc but not Fos rescue of PDGF signalling block caused by kinase-inactive Src
Barone, M. V., & Courtneidge, S. A. (1995) · Nature · doi:10.1038/378509a0 · Cited by 308
Self-citationSinibaldi, D., Wharton, W., Turkson, J., Bowman, T. L., Pledger, W. J., & Jove, R. (2000) · Oncogene · doi:10.1038/sj.onc.1203947 · Cited by 290
Self-citationTurkson, J., Bowman, T. L., Adnane, J., Zhang, Y., Djeu, J. Y., Sekharam, M., Frank, D. A., Holzman, L. B., Wu, J., Sebti, S. M., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.11.7519 · Cited by 259
Self-citationGould, K. L., & Hunter, T. R. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.8.3345 · Cited by 247
STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition
Fukada, T., Ohtani, T., Yoshida, Y., Shirogane, T., Nishida, K., Nakajima, K., Hibi, M., & Hirano, T. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6670 · Cited by 247
Roche, S., Koegl, M., Barone, M. V., Roussel, M. F., & Courtneidge, S. A. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.2.1102 · Cited by 244
Self-citationc-Src, Receptor Tyrosine Kinases, and Human Cancer
Biscardi, J. S., Tice, D. A., & Parsons, S. J. (1999) · Advances in cancer research · doi:10.1016/s0065-230x(08)60774-5 · Cited by 243
Mysterious liaisons: the relationship between c-Myc and the cell cycle
Obaya, Á. J., Mateyak, M. K., & Sedivy, J. M. (1999) · Oncogene · doi:10.1038/sj.onc.1202749 · Cited by 242
Self-citationSTAT proteins as novel targets for cancer therapy
Catlett-Falcone, R., Dalton, W. S., & Jove, R. (1999) · Current Opinion in Oncology · doi:10.1097/00001622-199911000-00010 · Cited by 185
Self-citationDifferential Complementation of Bcr-Abl Point Mutants with c-Myc
Afar, D., Goga, A., McLaughlin, J., Witte, O. N., & Sawyers, C. L. (1994) · Science · doi:10.1126/science.8153630 · Cited by 183
Kraker, A. J., Hartl, B. G., Amar, A. M., Barvian, M. R., Showalter, H. D., & Moore, C. W. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00405-6 · Cited by 140
Expression of Dominant-Negative Mutant DP-1 Blocks Cell Cycle Progression in G 1
Wu, C., Classon, M., Dyson, N. J., & Harlow, E. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3698 · Cited by 139
Broome, M. A., & Hunter, T. R. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.28.16798 · Cited by 137
Self-citationBesser, D., Bromberg, J., Darnell, J. E., Jr., & Hanafusa, H. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1401 · Cited by 123
Wang, Y.-Z., Wharton, W., Garcia, R., Kraker, A. J., Jove, R., & Pledger, W. J. (2000) · Oncogene · doi:10.1038/sj.onc.1203548 · Cited by 113
Self-citationHunter, T. (1985) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.54.1.897 · Cited by 109
Regulation of both apoptosis and cell survival by the v-Src oncoprotein
Johnson, D., Agochiya, M., Samejima, K., Earnshaw, W. C., Frame, M. C., & Wyke, J. A. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400700 · Cited by 82
Sachsenmaier, C., Sadowski, H. B., & Cooper, J. A. (1999) · Oncogene · doi:10.1038/sj.onc.1202694 · Cited by 66
Aziz, N. A., Cherwinski, H. M., & McMahon, M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1101 · Cited by 55
v-Src Generates a p53-Independent Apoptotic Signal
Webb, B. L., Jimenez, E., & Martin, G. S. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.24.9271-9280.2000 · Cited by 53
Broome, M. A., & Courtneidge, S. A. (2000) · Oncogene · doi:10.1038/sj.onc.1203608 · Cited by 45
Self-citationGould, K. L., & Hunter, T. R. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.8.3345-3356.1988 · Cited by 44
Bazarov, A., Adachi, S., Li, S. F., Mateyak, M. K., Wei, S., & Sedivy, J. M. (2001) · PubMed · Cited by 42
Self-citation
Research works printed but not linked: 4
- R Garcia, C L Yu, A Hudnall, R Catlett, K L Nelson, T Smithgall, D J Fujita, S P Ethier, R Jove Cell Growth Differ 8, 1267–1276 (1997).
- M K Mateyak, A J Obaya, S Adachi, J M Sedivy Cell Growth Differ 8, 1039–1048 (1997).
- G Niu, R Heller, R Catlett-Falcone, D Coppola, M Jaroszeski, W Dalton, R Jove, H Yu Cancer Res 59, 5059–5063 (1999).
- A V Bazarov, S Adachi, S F Li, M K Mateyak, S Wei, J M Sedivy Cancer Res 61, 1178–1186 (2001).
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Yu, H., & Jove, R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1275 · Cited by 2,278
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Yu, H., Kortylewski, M., & Pardoll, D. M. (2006) · Nature reviews. Immunology · doi:10.1038/nri1995 · Cited by 1,841
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Metadata
- Authors
- Bowman, T., Broome, M. A., Sinibaldi, D., Wharton, W., Pledger, W. J., Sedivy, J. M., Irby, R., Yeatman, T., Courtneidge, S. A., & Jove, R.
- Affiliations
- University of South Florida (US)
- Pfizer (United States) (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-06-12
- Volume
- 98
- Issue
- 13
- Pages
- 7319-7324
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC34666
- OpenAlex
- W2042794591
- Cited by
- 488
- References
- 54
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 8 · 2023: 24 · 2022: 12 · 2021: 13 · 2020: 12 · 2019: 13 · 2018: 13 · 2017: 20 · 2016: 15 · 2015: 24 · 2014: 21 · 2013: 20 · 2012: 30
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Moffitt Cancer Center
- National Cancer Institute (R01CA055652, CA-55652, CA 67360, R01CA067360)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- STAT3, c-Myc, v-Src, Src family kinases, platelet-derived growth factor, cell transformation, SU6656, STAT signaling, NIH3T3 cells, oncogenic transformation
- MeSH terms
- Animals, Cell Division, Cell Line, Transformed, Cell Transformation, Neoplastic, DNA-Binding Proteins, Gene Expression Regulation, Models, Biological, Platelet-Derived Growth Factor, Recombinant Proteins, Signal Transduction, Trans-Activators, Genes, myc, Proto-Oncogene Proteins c-myc, Genes, src, 3T3 Cells, STAT3 Transcription Factor, Mice
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