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  • Original Paper
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STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells

Abstract

Signal transduction and activator of transcription 3(STAT3) signaling is constitutively activated in various tumors, and is involved in cell survival and proliferation during oncogenesis. There are few reports, however, on the role of STAT3 signaling in gastric cancer. The aim of the present study was to clarify the role of STAT3 signaling in apoptosis and cellular proliferation in gastric cancer. Here we reported that STAT3 was constitutively activated in various human gastric cancer cells and its inhibition by ectopic dominant-negative STAT3 or Janus kinase inhibitor, tyrphostin AG490, induced apoptosis. Furthermore, STAT3 inhibition markedly decreased survivin expression, and forced expression of survivin rescued AGS cells from apoptosis induced by STAT3 inhibition. Although some reports demonstrated that the PI3K/Akt pathway regulates survivin expression, inhibition of the PI3K/Akt pathway did not affect survivin expression in AGS and MKN1 cells. Finally, activated form of STAT3, Tyr-705 phospho-stat3, was found in the nucleus of cancer cells in 11 of 40 (27.5%) human gastric cancer specimens. These findings suggest that constitutively activated STAT3 signaling supports gastric cancer cell survival in association with survivin expression.

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References

  • Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M and Kishimoto T . (1994). Cell, 77, 63–71.

  • Altieri DC . (2003). Nat. Rev. Cancer, 3, 46–54.

  • Ambrosini G, Adida C and Altieri DC . (1997). Nat. Med., 3, 917–921.

  • Aoki Y, Feldman GM and Tosato G . (2003). Blood, 101, 1535–1542.

  • Bisping G, Leo R, Wenning D, Dankbar B, Padro T, Kropff M, Scheffold C, Kroger M, Mesters RM, Berdel WE and Kienast J . (2003). Blood, 101, 2775–2783.

  • Bowman T, Garcia R, Turkson J and Jove R . (2000). Oncogene, 19, 2474–2488.

  • Bromberg JF . (2001). BioEssays, 23, 161–169.

  • Bromberg JF, Horvath CM, Besser D, Lathem WW and Darnell Jr. JE . (1998). Mol. Cell. Biol., 18, 2553–2558.

  • Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C and Darnell Jr JE . (1999). Cell, 98, 295–303.

  • Buettner R, Mora LB and Jove R . (2002). Clin. Cancer Res., 8, 945–954.

  • Burke WM, Jin X, Lin HJ, Huang M, Liu R, Reynolds RK and Lin J . (2001). Oncogene, 20, 7925–7934.

  • Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, Dalton WS and Jove R . (1999). Immunity, 10, 105–115.

  • Darnell Jr JE . (1997). Science, 277, 1630–1635.

  • Fukuda S and Pelus LM . (2001). Blood, 98, 2091–2100.

  • Gianani R, Jarboe E, Orlicky D, Frost M, Bobak J, Lehner R and Shroyer KR . (2001). Hum. Pathol., 32, 119–125.

  • Giri D, Ozen M and Ittmann M . (2001). Am. J. Pathol., 159, 2159–2165.

  • Horvath CM, Wen Z and Darnell Jr JE . (1995). Genes Dev., 9, 984–994.

  • Ikeguchi M and Kaibara N . (2002). Br. J. Cancer, 87, 883–887.

  • Izuishi K, Kato K, Ogura T, Kinoshita T and Esumi H . (2000). Cancer Res., 60, 6201–6207.

  • Kanai M, Konda Y, Nakajima T, Izumi Y, Kanda N, Nanakin A, Kubohara Y and Chiba T . (2003). Oncogene, 22, 548–554.

  • Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T and Tanigawa N . (1998). Cancer Res., 58, 5071–5074.

  • Konno R, Yamakawa H, Utsunomiya H, Ito K, Sato S and Yajima A . (2000). Mol. Hum. Reprod., 6, 529–534.

  • Kube D, Holtick U, Vockerodt M, Ahmadi T, Haier B, Behrmann I, Heinrich PC, Diehl V and Tesch H . (2001). Blood, 98, 762–770.

  • Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC and Altieri DC . (1998). Nature, 396, 580–584.

  • Marusawa H, Matsuzawa S, Welsh K, Zou H, Armstrong R, Tamm I and Reed JC . (2003). EMBO. J., 22, 2729–2740.

  • Monzo M, Rosell R, Felip E, Astudillo J, Sanchez JJ, Maestre J, Martin C, Font A, Barnadas A and Abad A . (1999). J. Clin. Oncol., 17, 2100–2104.

  • Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, Bowman T, Falcone R, Fairclough R, Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J and Jove R . (2002). Cancer Res., 62, 6659–6666.

  • Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, Kitaoka T, Fukada T, Hibi M and Hirano T . (1996). EMBO J., 15, 3651–3658.

  • Papapetropoulos A, Fulton D, Mahboubi K, Kalb RG, O'Connor DS, Li F, Altieri DC and Sessa WC . (2000). J. Biol. Chem., 275, 9102–9105.

  • Rahaman SO, Harbor PC, Chernova O, Barnett GH, Vogelbaum MA and Haque SJ . (2002). Oncogene, 21, 8404–8413.

  • Real PJ, Sierra A, De Juan A, Segovia JC, Lopez-Vega JM and Fernandez-Luna JL . (2002). Oncogene, 21, 7611–7618.

  • Ruff-Jamison S, Zhong Z, Wen Z, Chen K, Darnell Jr JE and Cohen S . (1994). J. Biol. Chem., 269, 21933–21935.

  • Sasse J, Hemmann U, Schwartz C, Schniertshauer U, Heesel B, Landgraf C, Schneider-Mergener J, Heinrich PC and Horn F . (1997). Mol. Cell. Biol., 17, 4677–4686.

  • Song JI and Grandis JR . (2000). Oncogene, 19, 2489–2495.

  • Swana HS, Grossman D, Anthony JN, Weiss RM and Altieri DC . (1999). N. Engl. J. Med., 341, 452–453.

  • Tran J, Master Z, Yu JL, Rak J, Dumont DJ and Kerbel RS . (2002). Proc. Natl. Acad. Sci. USA, 99, 4349–4354.

  • Vinkemeier U, Cohen SL, Moarefi I, Chait BT, Kuriyan J and Darnell Jr JE . (1996). EMBO J., 15, 5616–5626.

  • Werner M, Becker KF, Keller G and Hofler H . (2001). J. Cancer Res. Clin. Oncol., 127, 207–216.

  • Zaffaroni N, Pennati M, Colella G, Perego P, Supino R, Gatti L, Pilotti S, Zunino F and Daidone MG . (2002). Cell. Mol. Life Sci., 59, 1406–1412.

  • Zhang T, Otevrel T, Gao Z, Ehrlich SM, Fields JZ and Boman BM . (2001). Cancer Res., 61, 8664–8667.

  • Zhong Z, Wen Z and Darnell Jr JE . (1994a). Proc. Natl. Acad. Sci. USA, 91, 4806–4810.

  • Zhong Z, Wen Z and Darnell Jr JE . (1994b). Science, 264, 95–98.

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Acknowledgements

This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan (14770234). Clinical specimens were kindly provided by Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University.

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Correspondence to Hiroshi Seno.

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Kanda, N., Seno, H., Konda, Y. et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene 23, 4921–4929 (2004). https://doi.org/10.1038/sj.onc.1207606

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