publication . Article . 2010

Differential interleukin-6/Stat3 signaling as a function of cellular context mediates Ras-induced transformation

Katrina Podsypanina; Kenneth Leslie; Hao Ho; Lionel B. Ivashkiv; Marjan Berishaj; Jacqueline Bromberg; Sizhi P. Gao;
Open Access English
  • Published: 01 Oct 2010 Journal: Breast Cancer Research, volume 12, issue 5 (issn: 1465-542X, Copyright policy)
  • Publisher: Springer Nature
Abstract
Introduction Tyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is expressed in numerous cancers and is required for mediating tumorigenesis. Autocrine and paracrine interleukin (IL)-6 signaling is the principal mechanism by which Stat3 is persistently phosphorylated in epithelial tumors including breast, lung, colon and gastric cancer. The Ras oncogene mediates cellular transformation without evidence of pStat3 in cultured cells. However, non-tyrosine phosphorylated Stat3 was shown to function as a transcriptional activator, localize to the mitochondria and regulate ATP synthesis and mediate cell migration. Here we examined the ...
Subjects
free text keywords: Medicine(all), Cancer Research, Oncology, Research Article, Oncogene, STAT3 Transcription Factor, Paracrine signalling, Autocrine signalling, STAT3, biology.protein, biology, Interleukin, Signal transduction, STAT protein, Cell biology
Funded by
NIH| Role of Stat3 in Breast Cancer Tumorigenesis
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA087637-03
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| MOUSE GENETICS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
71 references, page 1 of 5

Clevenger, CV. Roles and regulation of stat family transcription factors in human breast cancer. Am J Pathol. 2004; 165: 1449-1460 [OpenAIRE] [PubMed]

Yu, H, Jove, R. The STATs of cancer--new molecular targets come of age. Nat Rev Cancer. 2004; 4: 97-105 [OpenAIRE] [PubMed] [DOI]

Darnell, JE. STATs and gene regulation. Science. 1997; 277: 1630-1635 [OpenAIRE] [PubMed] [DOI]

Bromberg, J. Stat proteins and oncogenesis. J Clin Invest. 2002; 109: 1139-1142 [OpenAIRE] [PubMed]

Diaz, N, Minton, S, Cox, C, Bowman, T, Gritsko, T, Garcia, R, Eweis, I, Wloch, M, Livingston, S, Seijo, E, Cantor, A, Lee, JH, Beam, CA, Sullivan, D, Jove, R, Muro-Cacho, CA. Activation of stat3 in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression. Clin Cancer Res. 2006; 12: 20-28 [PubMed] [DOI]

Berishaj, M, Gao, SP, Ahmed, S, Leslie, K, Al-Ahmadie, H, Gerald, WL, Bornmann, W, Bromberg, JF. Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer. Breast Cancer Res. 2007; 9: R32 [OpenAIRE] [PubMed] [DOI]

Schafer, ZT, Brugge, JS. IL-6 involvement in epithelial cancers. J Clin Invest. 2007; 117: 3660-3663 [OpenAIRE] [PubMed] [DOI]

Chiarle, R, Simmons, WJ, Cai, H, Dhall, G, Zamo, A, Raz, R, Karras, JG, Levy, DE, Inghirami, G. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nat Med. 2005; 11: 623-629 [OpenAIRE] [PubMed] [DOI]

Chan, KS, Sano, S, Kiguchi, K, Anders, J, Komazawa, N, Takeda, J, DiGiovanni, J. Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest. 2004; 114: 720-728 [OpenAIRE] [PubMed]

Ng, DC, Lin, BH, Lim, CP, Huang, G, Zhang, T, Poli, V, Cao, X. Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin. J Cell Biol. 2006; 172: 245-257 [OpenAIRE] [PubMed] [DOI]

Yang, J, Chatterjee-Kishore, M, Staugaitis, SM, Nguyen, H, Schlessinger, K, Levy, DE, Stark, GR. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 2005; 65: 939-947 [PubMed]

Yang, J, Liao, X, Agarwal, MK, Barnes, L, Auron, PE, Stark, GR. Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev. 2007; 21: 1396-1408 [OpenAIRE] [PubMed] [DOI]

Boguski, MS, McCormick, F. Proteins regulating Ras and its relatives. Nature. 1993; 366: 643-654 [OpenAIRE] [PubMed] [DOI]

Clair, T, Miller, WR, Cho-Chung, YS. Prognostic significance of the expression of a ras protein with a molecular weight of 21,000 by human breast cancer. Cancer Res. 1987; 47: 5290-5293 [PubMed]

Clark, GJ, Der, CJ. Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res Treat. 1995; 35: 133-144 [PubMed] [DOI]

71 references, page 1 of 5
Any information missing or wrong?Report an Issue