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2013 | 67 | 2 | 133–141
Article title

STAT3 – ukryty czynnik transkrypcyjny celem terapii przeciwnowotworowych

Content
Title variants
EN
STAT3 – Latent transciption factor for anti-cancer therapy
Languages of publication
PL
Abstracts
EN
STAT proteins belong to the transcriptional factors family, and each of them performs a unique function in extracellular signal transduction and in direct regulation of transcription. Their function is based on controlling genes expression, which is involved in cell survival, proliferation, chemoresistance and angiogenesis. Phosphorylated STAT3 is observed in 70% of human cancers. STAT3 as an oncogenic protein is constitutively activated in many primary human cancers by different cytokines as: IL-6 IL-7, IL-10, IL-20, leptin, granulocyte colony-stimulating factor (G-CSF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and oncogenic proteins such as Src and Ras. Moreover, STAT3 can be activated by receptor and nonreceptor tyrosine kinases such as: epidermal growth factor receptor kinase (EGFR), activated Janus kinase (JAK) or kinase regulating extracellular signals (ERK). An important role of STAT3 is the regulation of cancer cells autonomous properties. The blocking of STAT3 expression in human cancer cells inhibits proliferation in vitro and cancer progression in vivo. To inhibit gene expression of STAT3, antisense oligonucleotides, rybozimes and DNAzymes can be used. The STAT3 protein can be blocked by tyrosine kinase inhibitors, negative dominants for the STAT3 protein, complementary to small nonpeptide particle drugs. Among the newest methods of gene expression regulation is the RNA – RNAi method of interference.
PL
Białka STAT (signal transducer and activator of transcription – przekaźnik sygnału i aktywator transkrypcji) to rodzina czynników transkrypcyjnych, z których każdy pełni unikalną funkcję w przekazywaniu sygnałów zewnątrzko-mórkowych oraz bezpośrednim regulowaniu transkrypcji. Ich funkcja polega na kontroli ekspresji genów, które zaangażowane są w przeżycie komórek, proliferację, chemiooporność oraz angiogenezę. Ufosforylowany STAT3 obserwuje się w blisko 70% ludzkich nowotworów. Pełniąc rolę białka onkogennego ulega on konstytutywnej aktywacji w wielu pierwotnych nowotworach u ludzi, będąc aktywowanym przez wiele różnych cytokin, takich jak IL-6 IL-7, IL-10, IL-20, leptyna, czynnik stymulujący wzrost kolonii granulocytów (granulocyte colony stimulating factor – G-CSF), epidermalny czynnik wzrostu (epidermal growth factor – EGF), płytkowy czynnik wzrostu (platelet-derived growth factor – PDGF), a także białka onkogenne, m.in. Src i Ras. Ponadto STAT3 może być aktywowany poprzez receptorowe i niereceptorowe kinazy tyrozynowe, takie jak: kinaza receptora epidermalnego czynnika wzrostu (kinase of epidermal growth factor receptor – EGFR), aktywowana kinaza Janus (activated Janus kinase – JAK), kinazy regulujące sygnały zewnątrzkomórkowe (kinases regulating extracellular signals – ERK). Jego istotną funkcją jest regulacja autonomicznych właściwości komórek nowotworowych. Blokowanie ekspresji STAT3 w ludzkich komórkach nowotworowych hamuje proliferację in vitro oraz progresję nowotworów in vivo. W celu wyciszenia ekspresji genów STAT3 można wykorzystać oligonukleotydy antysensowe, rybozymy i DNAzymy. Samo białko STAT3 można zablokować wykorzystując inhibitory kinazy tyrozynowej, dominanty negatywne wobec białka STAT3, komplementarne wobec leków małe niepeptydowe cząsteczki. Wśród najnowszych metod regulacji ekspresji genów znajduje się metoda wykorzystująca proces interferencji RNA – RNAi.
Discipline
Year
Volume
67
Issue
2
Pages
133–141
Physical description
References
  • 1. Deng J.Y., Sun D., Liu X.Y., Pan Y., Liang H. STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer. World J. Gastroenterol. 2010; 16: 5380–5387.
  • 2. Badr G., Mohany M., Abu-Tarboush F. Thymoquinone decreases F-actin polymerization and the proliferation of human multiple myeloma cells by suppressing STAT3 phosphorylation and Bcl2/Bcl-XL expression. Lipids Health Dis. 2011; 10: 236.
  • 3. Egwuagu C.E. STAT3 in CD4+ T helper cell differentiation and inflammatory diseases. Cytokine 2009; 47(3): 149–156.
  • 4. Deng J., Grande F., Neamati N. Small molecule inhibitors of STAT3 signaling pathway. Curr. Cancer Drug Targets 2007; 7: 91–107.
  • 5. Schick N. STAT3 and tumor cell proliferation. Basel 2004; 10.
  • 6. Walker S.R., Chaudhury M., Frank D.A. STAT3 Inhibition by microtubule-targeted drugs: dual molecular effects of chemotherapeutic agents. Mol Cell Pharmacol. 2011; 3: 13–19.
  • 7. Calo V., Migliavacca M., Bazan V. i wsp. STAT proteins: from normal control of cellular events to tumorigenesis. J. Cell. Physiol. 2003; 197: 157–168.
  • 8. Sato T., Neilson L.M., Peck A.R. i wsp. Signal transducer and activator of transcription-3 and breast cancer prognosis. Am. J. Cancer Res. 2011; 1: 347–355.
  • 9. Lassmann S., Schuster I., Walch A. i wsp. STAT3 mRNA and protein expression in colorectal cancer: effects on STAT3-inducible targets linked to cell survival and proliferation. J. Clin. Pathol. 2007; 60: 173–179.
  • 10. Haviland R., Eschrich S., Bloom G., Ma Y., Minton S. Necdin, a negative growth regulator, is a novel STAT3 target gene down-regulated in human cancer. PLoS ONE 2011; 6(10): e24923.
  • 11. Zammarchia F., Stanchinab E., Bournazouc E. i wsp. Antitumorigenic potential of STAT3 alternative splicing modulation. PNAS 2011; 43: 17779–17784.
  • 12. Miranda C., Fumagalli T., Anania M.C. i wsp. Role of STAT3 in in vitro transformation triggered by TRK oncogenes. PLoS ONE. 2010; 5(3): e9446.
  • 13. Kortylewski M., Xin H., Kujawski M. i wsp. Regulation of the IL-23 and IL-12 balance by STAT3 signaling in the tumor microenvironment. Cancer Cell 2009; 15: 114–123.
  • 14. Shao H., Quintero A.J., Tweardy D.J. Identification and characterization of cis elements in the STAT3 gene regulating STAT3 alpha and STAT3 beta messenger RNA splicing. Blood 2001; 98: 3853–3856.
  • 15. Azare J., Doane A., Leslie K., Chang Q., Berishaj M. (2011) Stat3 mediates expression of Autotaxin in breast cancer. PLoS ONE 6(11): e27851.
  • 16. Chen Y., Deng J., Fujimoto J. i wsp. Gprc5a deletion enhances the transformed phenotype in normal and malignant lung epithelial cells by eliciting persistent Stat3 signaling induced by autocrine leukemia inhibitory factor. Cancer Res. 2010; 70: 8917–8926.
  • 17. Kusaba T., Nakayama T., Yamazumi K. i wsp. Activation of STAT3 is a marker of poor prognosis in human colorectal cancer. Oncol Rep. 2006; 15: 1445–1451.
  • 18. Lin L., Deangelis S., Foust E. i wsp. A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol. Cancer. 2010; 9: 217.
  • 19. Levy D. E., Lee C. What does STAT3 do? J. Clin. Invest. 2002; 109: 1143–1148.
  • 20. Germain G., Frank D.A. Targeting the cytoplasmic and nuclear functions of signal transducers and activators of transcription 3 for cancer therapy. Clin. Cancer Res. 2007; 13: 5665–5669.
  • 21. Kortylewski M., Yu H. Role of STAT3 in suppressing anti-tumor immunity. Curr Opin Immunol. 2008; 20: 228–233.
  • 22. Yang J., Chatterjee-Kishore M., Staugaitis S.M. i wsp. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 2005; 65: 939–947.
  • 23. Jarnicki A., Putoczki T., Ernst M. RSTAT3: linking inflammation to epithelial cancer – more than a "gut" feeling? Cell Div. 2010; 5(14): 1–15.
  • 24. Brantley E.C., Benveniste E.N. Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol. Cancer Res. 2008; 6: 675–684.
  • 25. Huang C., Yang G., Jiang T., Cao J., Huang K., Qiu Z. Down- regulation of STAT3 expression by vector-based small interfering RNA inhibits pancreatic cancer growth. World J. Gastroenterol. 2011; 17: 2992–3001.
  • 26. Yang Z., Cai J., Xie S. i wsp. Therapeutic effects of signal transducer and activator of transcription 3 siRNA on human breast cancer in xenograft mice. Chin. Med. J. 2011; 124: 1854–1861.
  • 27. Hai L., Huang C., Huang Ki., Wu Wd., Jiang T. STAT3 Knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice. PLoS ONE 2011; 6(10): e25941.
  • 28. Bollrath J., Phesse T.J., V. von Burstin A. i wsp. gp130-mediated STAT3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 2009; 15: 91–102.
  • 29. Aggarwal B.B., Kunnumakkara A.B., Harikumar K.B. i wsp. Signal transducer and activator of transcription-3, inflammation, and cancer. How intimate is the relationship? Ann. N. Y. Acad. Sci. 2009; 1171: 59–76.
Document Type
article
Publication order reference
YADDA identifier
bwmeta1.element.psjd-7640115a-5082-4a1c-a594-48412c78a7fb
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