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Review Open Access

Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review)

  • Authors:
    • Yael Delgado‑Ramirez
    • Vaneesa Colly
    • Giovanni Villanueva Gonzalez
    • Sonia Leon‑Cabrera
  • View Affiliations / Copyright

    Affiliations: Laboratory of Oncoimmunology, Biomedical Research Unit, National Autonomous University of Mexico, Tlalnepantla, CP 54090, Mexico, Medical School, Faculty of Superior Studies Iztacala, National Autonomous University of Mexico, Tlalnepantla, CP 54090, Mexico
    Copyright: © Delgado‑Ramirez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 455-464
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    Published online on: May 13, 2020
       https://doi.org/10.3892/ol.2020.11614
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Abstract

Signal transducer and activator of transcription 6 (STAT6) is a member of the STAT family of proteins that serve key roles in the initiation of tumorigenesis and malignant transformation. STAT6 is highly expressed in several types of cancer, including breast, pancreatic, prostate and colorectal cancer. STAT6 transduces signals in response to the binding of interleukin (IL)‑4 and IL‑13 to their receptors and regulates the expression of genes involved in the immune response, cell survival, tumor proliferation and metastasis. Patients with colorectal cancer exhibit high STAT6 activity in the colonic epithelium, and STAT6 expression is associated with lower survival rates, lymph node metastasis, changes in the epithelial barrier function and alterations in the inflammatory response. A number of studies investigating experimental models and cancer cell lines have revealed that STAT6 is associated with tumor growth and development, as well as with increased invasion and metastasis, suggesting that STAT6 inhibition may serve as a novel therapeutic strategy in colon cancer. The present review summarizes the evidence with regard to the implications of STAT6 in cancer biology and the direct and indirect effects on colon tumor transformation. Furthermore, the current treatment strategies targeting the IL‑4/IL‑13/STAT6 axis in colon cancer are discussed.
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1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJ and Watanabe T: Colorectal cancer. Nat Rev Dis Primers. 1:150652015. View Article : Google Scholar : PubMed/NCBI

3 

West NR, McCuaig S, Franchini F and Powrie F: Emerging cytokine networks in colorectal cancer. Nat Rev Immunol. 15:615–629. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Yu H, Pardoll D and Jove R: STATs in cancer inflammation and immunity: A leading role for STAT3. Nat Rev Cancer. 9:798–809. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Hebenstreit D, Wirnsberger G, Horejs-Hoeck J and Duschl A: Signaling mechanisms, interaction partners, and target genes of STAT6. Cytokine Growth Factor Rev. 17:173–188. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Chua KH, Ng JG, Ng CC, Hilmi I, Goh KL and Kee BP: Association of NOD1, CXCL16, STAT6 and TLR4 gene polymorphisms with Malaysian patients with Crohn's disease. Peerj. 4:e18432016. View Article : Google Scholar : PubMed/NCBI

7 

Klein W, Tromm A, Folwaczny C, Hagedorn M, Duerig N, Epplen J, Schmiegel W and Griga T: The G2964A polymorphism of the STAT6 gene in inflammatory bowel disease. Dig Liver Dis. 37:159–161. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Xia B, Crusius JB, Wu J, Zwiers A, van Bodegraven AA and Pena AS: Signal transducer and activator of transcription 6 gene G2964A polymorphism and inflammatory bowel disease. Clin Exp Immunol. 131:446–450. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Mueller TD, Zhang JL, Sebald W and Duschl A: Structure, binding, and antagonists in the IL-4/IL-13 receptor system. Biochim Biophys Acta. 1592:237–250. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Murata T, Noguchi PD and Puri RK: Receptors for interleukin (IL)-4 do not associate with the common gamma chain, and IL-4 induces the phosphorylation of JAK2 tyrosine kinase in human colon carcinoma cells. J Biol Chem. 270:30829–30836. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Sengupta S, Thaci B, Crawford AC and Sampath P: Interleukin-13 receptor alpha 2-targeted glioblastoma immunotherapy. Biomed Res Int. 2014:9521282014. View Article : Google Scholar : PubMed/NCBI

12 

Mikita T, Campbell D, Wu P, Williamson K and Schindler U: Requirements for interleukin-4-induced gene expression and functional characterization of Stat6. Mol Cell Biol. 16:5811–5820. 1996. View Article : Google Scholar : PubMed/NCBI

13 

Gupta S, Jiang M and Pernis AB: IFN-alpha activates Stat6 and leads to the formation of Stat2:Stat6 complexes in B cells. J Immunol. 163:3834–3841. 1999.PubMed/NCBI

14 

Dickensheets H, Vazquez N, Sheikh F, Gingras S, Murray PJ, Ryan JJ and Donnelly RP: Suppressor of cytokine signaling-1 is an IL-4-inducible gene in macrophages and feedback inhibits IL-4 signaling. Genes Immun. 8:21–27. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Li Y, Deuring J, Peppelenbosch MP, Kuipers EJ, de Haar C and van der Woude CJ: STAT1, STAT6 and adenosine 3′,5′-cyclic monophosphate (cAMP) signaling drive SOCS3 expression in inactive ulcerative colitis. Mol Med. 18:1412–1419. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Hanson EM, Dickensheets H, Qu CK, Donnelly RP and Keegan AD: Regulation of the dephosphorylation of Stat6. Participation of Tyr-713 in the interleukin-4 receptor alpha, the tyrosine phosphatase SHP-1, and the proteasome. J Biol Chem. 278:3903–3911. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Lu X, Malumbres R, Shields B, Jiang X, Sarosiek KA, Natkunam Y, Tiganis T and Lossos IS: PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling. Blood. 112:4098–4108. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Chen W, Daines MO and Hershey GK: Methylation of STAT6 modulates STAT6 phosphorylation, nuclear translocation, and DNA-binding activity. J Immunol. 172:6744–6750. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Di Stefano AB, Iovino F, Lombardo Y, Eterno V, Höger T, Dieli F, Stassi G and Todaro M: Survivin is regulated by interleukin-4 in colon cancer stem cells. J Cell Physiol. 225:555–561. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Huang F, Wang D, Yao YL and Wang M: PDGF signaling in cancer progression. Int J Clin Exp Med. 10:9918–9929. 2017.

21 

Patel BK, Wang LM, Lee CC, Taylor WG, Pierce JH and LaRochelle WJ: Stat6 and Jak1 are common elements in platelet-derived growth factor and interleukin-4 signal transduction pathways in NIH 3T3 fibroblasts. J Biol Chem. 271:22175–22182. 1996. View Article : Google Scholar : PubMed/NCBI

22 

Ingram JL, Antao-Menezes A, Mangum JB, Lyght O, Lee PJ, Elias JA and Bonner JC: Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts. J Immunol. 177:4141–4148. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Jess T, Rungoe C and Peyrin-Biroulet L: Risk of colorectal cancer in patients with ulcerative colitis: A meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol. 10:639–645. 2012. View Article : Google Scholar : PubMed/NCBI

24 

von Roon AC, Reese G, Teare J, Constantinides V, Darzi AW and Tekkis PP: The risk of cancer in patients with Crohn's disease. Dis Colon Rectum. 50:839–855. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Rosen MJ, Frey MR, Washington MK, Chaturvedi R, Kuhnhein LA, Matta P, Revetta FL, Wilson KT and Polk DB: STAT6 activation in ulcerative colitis: A new target for prevention of IL-13-induced colon epithelial cell dysfunction. Inflamm Bowel Dis. 17:2224–2234. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Wang CG, Ye YJ, Yuan J, Liu FF, Zhang H and Wang S: EZH2 and STAT6 expression profiles are correlated with colorectal cancer stage and prognosis. World J Gastroenterol. 16:2421–2427. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, Berger A, Bruneval P, Fridman WH, Pagès F and Galon J: Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 71:1263–1271. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Formentini A, Braun P, Fricke H, Link KH, Henne-Bruns D and Kornmann M: Expression of interleukin-4 and interleukin-13 and their receptors in colorectal cancer. Int J Colorectal Dis. 27:1369–1376. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Rosen MJ, Chaturvedi R, Washington MK, Kuhnhein LA, Moore PD, Coggeshall SS, McDonough EM, Weitkamp JH, Singh AB, Coburn LA, et al: STAT6 deficiency ameliorates severity of oxazolone colitis by decreasing expression of claudin-2 and Th2-inducing cytokines. J Immunol. 190:1849–1858. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Hoving JC, Kirstein F, Nieuwenhuizen NE, Fick LC, Hobeika E, Reth M and Brombacher F: B Cells that produce immunoglobulin E mediate Colitis in BALB/c mice. Gastroenterology. 142:96–108. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Buzza MS, Johnson TA, Conway GD, Martin EW, Mukhopadhyay S, Shea-Donohue T and Antalis TM: Inflammatory cytokines down-regulate the barrier-protective prostasin-matriptase proteolytic cascade early in experimental colitis. J Biol Chem. 292:10801–10812. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Shajib MS, Wang HQ, Kim JJ, Sunjic I, Ghia JE, Denou E, Collins M, Denburg JA and Khan WI: Interleukin 13 and Serotonin: Linking the immune and endocrine systems in murine models of intestinal inflammation. PLoS One. 8:e727742013. View Article : Google Scholar : PubMed/NCBI

33 

Leon-Cabrera SA, Molina-Guzman E, Delgado-Ramirez YG, Vázquez-Sandoval A, Ledesma-Soto Y, Pérez-Plasencia CG, Chirino YI, Delgado-Buenrostro NL, Rodríguez-Sosa M, Vaca-Paniagua F, et al: Lack of STAT6 attenuates inflammation and drives protection against early steps of colitis-associated colon cancer. Cancer Immunol Res. 5:385–396. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Jayakumar A and Bothwell ALM: Stat6 promotes intestinal tumorigenesis in a mouse model of adenomatous polyposis by expansion of MDSCs and inhibition of cytotoxic CD8 response. Neoplasia. 19:595–605. 2017. View Article : Google Scholar : PubMed/NCBI

35 

De Oliveira T, Ramakrishnan M, Diamanti MA, Ziegler PK, Brombacher F and Greten FR: Loss of Stat6 affects chromatin condensation in intestinal epithelial cells causing diverse outcome in murine models of inflammation-associated and sporadic colon carcinogenesis. Oncogene. 38:1787–1801. 2019. View Article : Google Scholar : PubMed/NCBI

36 

Wick EC, LeBlanc RE, Ortega G, Robinson C, Platz E, Pardoll DM, Iacobuzio-Donahue C and Sears CL: Shift from pStat6 to pStat3 predominance is associated with inflammatory bowel disease-associated dysplasia. Inflamm Bowel Dis. 18:1267–1274. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Cao H, Zhang J, Liu H, Wan L, Zhang H, Huang Q, Xu E and Lai M: IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells. Oncotarget. 7:61183–61198. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Jiang L, Cheng Q, Zhang B and Zhang M: IL-13 induces the expression of 11βHSD2 in IL-13Rα2 dependent manner and promotes the malignancy of colorectal cancer. Am J Transl Res. 8:1064–1072. 2016.PubMed/NCBI

39 

Barderas R, Bartolome RA, Fernandez-Acenero MJ, Torres S and Casal JI: High expression of IL-13 receptor α2 in colorectal cancer is associated with invasion, liver metastasis, and poor prognosis. Cancer Res. 72:2780–2790. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Chen J, Gong C, Mao H, Li Z, Fang Z, Chen Q, Lin M, Jiang X, Hu Y, Wang W, et al: E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells. Int J Oncol. 53:567–578. 2018.PubMed/NCBI

41 

Todaro M, Lombardo Y, Francipane MG, Alea MP, Cammareri P, Iovino F, Di Stefano AB, Di Bernardo C, Agrusa A, Condorelli G, et al: Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4. Cell Death Differ. 15:762–772. 2008. View Article : Google Scholar : PubMed/NCBI

42 

Liu H, Antony S, Roy K, Juhasz A, Wu Y, Lu J, Meitzler JL, Jiang G, Polley E and Doroshow JH: Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation of human colon cancer cells. Oncotarget. 8:38113–38135. 2017. View Article : Google Scholar : PubMed/NCBI

43 

Kanai T, Watanabe M, Hayashi A, Nakazawa A, Yajima T, Okazawa A, Yamazaki M, Ishii H and Hibi T: Regulatory effect of interleukin-4 and interleukin-13 on colon cancer cell adhesion. Br J Cancer. 82:1717–1723. 2000.PubMed/NCBI

44 

Binnemars-Postma K, Bansal R, Storm G and Prakash J: Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer. FASEB J. 32:969–978. 2018. View Article : Google Scholar : PubMed/NCBI

45 

Linde N, Lederle W, Depner S, van Rooijen N, Gutschalk CM and Mueller MM: Vascular endothelial growth factor-induced skin carcinogenesis depends on recruitment and alternative activation of macrophages. J Pathol. 227:17–28. 2012. View Article : Google Scholar : PubMed/NCBI

46 

Ostrand-Rosenberg S, Sinha P, Clements V, Dissanayake SI, Miller S, Davis C and Danna E: Signal transducer and activator of transcription 6 (Stat6) and CD1: Inhibitors of immunosurveillance against primary tumors and metastatic disease. Cancer Immunol Immunother. 53:86–91. 2004. View Article : Google Scholar : PubMed/NCBI

47 

Conticello C, Pedini F, Zeuner A, Patti M, Zerilli M, Stassi G, Messina A, Peschle C and De Maria R: IL-4 protects tumor cells from anti-CD95 and chemotherapeutic agents via up-regulation of antiapoptotic proteins. J Immunol. 172:5467–5477. 2004. View Article : Google Scholar : PubMed/NCBI

48 

Francipane MG, Alea MP, Lombardo Y, Todaro M, Medema JP and Stassi G: Crucial role of interleukin-4 in the survival of colon cancer stem cells. Cancer Res. 68:4022–4025. 2008. View Article : Google Scholar : PubMed/NCBI

49 

Li BH, Yang XZ, Li PD, Yuan Q, Liu XH, Yuan J and Zhang WJ: IL-4/Stat6 activities correlate with apoptosis and metastasis in colon cancer cells. Biochem Biophys Res Commun. 369:554–560. 2008. View Article : Google Scholar : PubMed/NCBI

50 

Li BH, Xu SB, Li F, Zou XG, Saimaiti A, Simayi D, Wang YH, Zhang Y, Yuan J and Zhang WJ: Stat6 activity-related Th2 cytokine profile and tumor growth advantage of human colorectal cancer cells in vitro and in vivo. Cell Signal. 24:718–725. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Volonte A, Di Tomaso T, Spinelli M, Todaro M, Sanvito F, Albarello L, Bissolati M, Ghirardelli L, Orsenigo E, Ferrone S, et al: Cancer-initiating cells from colorectal cancer patients escape from T cell-mediated immunosurveillance in vitro through membrane-bound IL-4. J Immunol. 192:523–532. 2014. View Article : Google Scholar : PubMed/NCBI

52 

Cosin-Roger J, Ortiz-Masia D, Calatayud S, Hernandez C, Esplugues JV and Barrachina MD: The activation of Wnt signaling by a STAT6-dependent macrophage phenotype promotes mucosal repair in murine IBD. Mucosal Immunol. 9:986–998. 2016. View Article : Google Scholar : PubMed/NCBI

53 

Mendoza-Rodriguez MG, Sanchez-Barrera CA, Callejas BE, García-Castillo V, Beristain-Terrazas DL, Delgado-Buenrostro NL, Chirino YI, León-Cabrera SA, Rodríguez-Sosa M, Gutierrez-Cirlos EB, et al: Use of STAT6 Phosphorylation inhibitor and trimethylglycine as new adjuvant therapies for 5-fluorouracil in colitis-associated tumorigenesis. Int J Mol Sci. 21(pii): E21302020. View Article : Google Scholar : PubMed/NCBI

54 

Nappo G, Handle F, Santer FR, McNeill RV, Seed RI, Collins AT, Morrone G, Culig Z, Maitland NJ and Erb HHH: The immunosuppressive cytokine interleukin-4 increases the clonogenic potential of prostate stem-like cells by activation of STAT6 signalling. Oncogenesis. 6:e3422017. View Article : Google Scholar : PubMed/NCBI

55 

Xu K, Tao W and Su Z: Propofol prevents IL-13-induced epithelial-mesenchymal transition in human colorectal cancer cells. Cell Biol Int. 42:985–993. 2018. View Article : Google Scholar : PubMed/NCBI

56 

Healey GD, Lockridge JA, Zinnen S, Hopkin JM, Richards I and Walker W: Development of pre-clinical models for evaluating the therapeutic potential of candidate siRNA targeting STAT6. PLoS One. 9:e903382014. View Article : Google Scholar : PubMed/NCBI

57 

Bartolome RA, Jaen M and Casal JI: An IL13Rα2 peptide exhibits therapeutic activity against metastatic colorectal cancer. Br J Cancer. 119:940–949. 2018. View Article : Google Scholar : PubMed/NCBI

58 

Gharib AF, Shalaby SM, Raafat N, Fawzy WMS and Abdel Hakim NH: Assessment of neutralizing interleukin-4 effect on CD133 gene expression in colon cancer cell line. Cytokine. 97:66–72. 2017. View Article : Google Scholar : PubMed/NCBI

59 

Todaro M, Perez Alea M, Scopelliti A, Medema JP and Stassi G: IL-4-mediated drug resistance in colon cancer stem cells. Cell Cycle. 7:309–313. 2008. View Article : Google Scholar : PubMed/NCBI

60 

Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP and Stassi G: Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 1:389–402. 2007. View Article : Google Scholar : PubMed/NCBI

61 

Rivankar S: An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther. 10:853–858. 2014. View Article : Google Scholar : PubMed/NCBI

62 

Yang CY, Liu HW, Tsai YC, Tseng JY, Liang SC, Chen CY, Lian WN, Wei MC, Lu M, Lu RH, et al: Interleukin-4 receptor-targeted liposomal doxorubicin as a model for enhancing cellular uptake and antitumor efficacy in murine colorectal cancer. Cancer Biol Ther. 16:1641–1650. 2015. View Article : Google Scholar : PubMed/NCBI

63 

O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y and Laurence A: Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 72 (Suppl 2):ii111–ii115. 2013. View Article : Google Scholar : PubMed/NCBI

64 

Regenbogen T, Chen L, Trinkaus K, Wang-Gillam A, Tan BR, Amin M, Pedersen KS, Park H, Suresh R, Lim KH, et al: Pacritinib to inhibit JAK/STAT signaling in refractory metastatic colon and rectal cancer. J Gastrointest Oncol. 8:985–989. 2017. View Article : Google Scholar : PubMed/NCBI

65 

Pardanani A and Tefferi A: How I treat myelofibrosis after failure of JAK inhibitors. Blood. 132:492–500. 2018. View Article : Google Scholar : PubMed/NCBI

66 

Fogelman D, Cubillo A, Garcia-Alfonso P, Mirón MLL, Nemunaitis J, Flora D, Borg C, Mineur L, Vieitez JM, Cohn A, et al: Randomized, double-blind, phase two study of ruxolitinib plus regorafenib in patients with relapsed/refractory metastatic colorectal cancer. Cancer Med. 7:5382–5393. 2018. View Article : Google Scholar : PubMed/NCBI

67 

Shimaoka H, Takeno S, Maki K, Sasaki T, Hasegawa S and Yamashita Y: A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer. Oncol Lett. 14:3019–3027. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Delgado‑Ramirez Y, Colly V, Villanueva Gonzalez G and Leon‑Cabrera S: Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review). Oncol Lett 20: 455-464, 2020.
APA
Delgado‑Ramirez, Y., Colly, V., Villanueva Gonzalez, G., & Leon‑Cabrera, S. (2020). Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review). Oncology Letters, 20, 455-464. https://doi.org/10.3892/ol.2020.11614
MLA
Delgado‑Ramirez, Y., Colly, V., Villanueva Gonzalez, G., Leon‑Cabrera, S."Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review)". Oncology Letters 20.1 (2020): 455-464.
Chicago
Delgado‑Ramirez, Y., Colly, V., Villanueva Gonzalez, G., Leon‑Cabrera, S."Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review)". Oncology Letters 20, no. 1 (2020): 455-464. https://doi.org/10.3892/ol.2020.11614
Copy and paste a formatted citation
x
Spandidos Publications style
Delgado‑Ramirez Y, Colly V, Villanueva Gonzalez G and Leon‑Cabrera S: Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review). Oncol Lett 20: 455-464, 2020.
APA
Delgado‑Ramirez, Y., Colly, V., Villanueva Gonzalez, G., & Leon‑Cabrera, S. (2020). Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review). Oncology Letters, 20, 455-464. https://doi.org/10.3892/ol.2020.11614
MLA
Delgado‑Ramirez, Y., Colly, V., Villanueva Gonzalez, G., Leon‑Cabrera, S."Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review)". Oncology Letters 20.1 (2020): 455-464.
Chicago
Delgado‑Ramirez, Y., Colly, V., Villanueva Gonzalez, G., Leon‑Cabrera, S."Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review)". Oncology Letters 20, no. 1 (2020): 455-464. https://doi.org/10.3892/ol.2020.11614
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