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  • Original Paper
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STAT signaling in head and neck cancer

Oncogene volume 19, pages 2489–2495 (2000)Cite this article

Abstract

The upper aerodigestive tract is predisposed to the formation of multiple primary tumors due to field cancerization. TGF-α/EGFR autocrine signaling appears to play an important role in squamous cell carcinoma of the head and neck (SCCHN) and upregulation of TGF-α and EGFR is an early event in SCCHN carcinogenesis. STAT proteins, including Stat3, are activated by TGF-α and EGFR and strategies that downmodulate TGF-α or EGFR inhibit SCCHN cell proliferation and abrogate Stat3 activation. Targeting Stat3 leads to SCCHN growth inhibition, increases apoptosis and a downmodulation of Bcl-xL expression in head and neck tumors. These studies support the role of Stat3 as an oncogene, which is activated early in SCCHN carcinogenesis, and efforts to understand EGFR-mediated Stat3 signaling could facilitate novel strategies that will interfere with this growth promoting pathway.

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References

  • American Joint Committee on Cancer . Manual for Staging of Cancer, 2nd edn 1983 Philadelphia Lippincott pp 25–54

  • Becker D, Meier CB and Herlyn M . 1989 EMBO J 8: 3685–3691

  • Becker D, Lee PL, Rodeck U and Herlyn M . 1992 Oncogene 7: 2303–2313

  • Bos M, Mendelsohn J, Kim YM, Albanell J, Fry DW and Baselga J . 1997 Clin Cancer Res 3: 2099–2106

  • Boyle P, Macfarlane GJ, Zheng T, Maisonneuve P, Evstifeeva T and Scully C . 1992 Curr Opin Oncol 4: 471–477

  • Bromberg JF, Wrzeszczynska MH, Zhao Y, Pestrell RG, Albanese C and Darnell JE . 1999 Cell 98: 295–303

  • Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, Corio R, Lee D, Greenberg B, Koch W and Sidransky D . 1996 Cancer Res 56: 2488–2492

  • Cancer Statistics 1990 New York American Cancer Society

  • Carpenter G . 1992 FASEB J 6: 3283–3289

  • Castigliano SG . 1968 J Am Dent Assoc 77: 580–585

  • Catlett-Falcone R, Landowski TH, Oshiro NM, 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

  • Coffer PJ and Kruijer W . 1995 Biochem Biophys Res Comm 210: 74–81

  • Darnell JE . 1997 Science 277: 1630–1635

  • David M, Wong L, Flavell R, Thompson SA, Wells A, Larner AC and Johnson GR . 1996 J Biol Chem 271: 9185–9188

  • DeGiovanni C, Landuzzi L, Frabetti F, Nicoletti G, Griffoni C, Rossi I, Mazzotti M, Scotto L, Nanni P and Lollini PL . 1996 Cancer Res 56: 3898–3901

  • DeMichele MA, Davis AL, Hunt JD, Landreneau RJ and Siegfried JM . Am J Resp Cell Mol Biol 11: 66–74

  • Dhooge IJ, De Vos M and Van Cauwenberge PB . 1998 Laryngoscope 108: 250–256

  • Dimery IW and Hong WK . 1993 J Natl Cancer Inst 85: 95–111

  • Earp HS, Dawson TL, Li X and Yu H . 1995 Breast Cancer Res Treat 35: 115–132

  • Eishbruch A, Blick M, Lee JS, Sacks PG and Gutterman J . 1987 Cancer Res 47: 3603–3605

  • Fry DW, Kraker AJ, McMichael A, Ambroso LA, Nelson JM, Leopold WR, Connors RW and Bridges AJ . 1994 Science 265: 1093–1095

  • Garcia R and Jove R . 1998 J Biomed Sci 5: 79–85

  • Garcia R, Yu CL, Hudnall A, Catlett R, Nelson KL, Smithgall T, Fujita DJ, Ethier SP and Jove R . 1997 Cell Growth Differ 8: 1267–1276

  • He Y, Zeng Q, Drenning SD, Melham MF, Tweardy DJ, Huang L and Grandis JR . 1998 J Natl Cancer Inst 90: 1080–1087

  • Hernandez-Sotomayor SMT and Carpenter G . 1992 Membr Biol 128: 81–89

  • Hierholzer C, Kalff JC, Omert L, Tsukada K, Loeffert JE, Watkins SC, Billiar TR and Tweardy DJ . 1998 Am J Physiol 275: L611–L621

  • Hong WK and Bromer R . 1983 N Engl J Med 308: 75–79

  • Ihle JN . 1996 Cell 84: 331–334

  • Ishitoya J, Toriyama O, Oguchi N, Kitamura K, Ohshima M, Asano K and Yamamoto T . 1989 Br J Cancer 59: 559–562

  • James R and Bradshaw RA . 1984 Annu Rev Biochem 53: 259–292

  • Jovanovich A, Van der Tol IGH and Kostense PJ . 1994 Eur J Cancer 30B: 225–229

  • Kawamoto T, Takahashi K and Nishi M . 1991 Jpn J Cancer Res 83: 403–410

  • Kumar V, Bustin SA and McKay IA . 1995 J Cell Biol Int 19: 373–388

  • Larson JT, Adams GL and Fattah HA . 1990 Otolaryngol-Head Neck Surg 103: 14–24

  • Leaman DW, Pisharody S, Flickinger TW, Commane MA, Schlessinger J, Kerr IM, Levy DE and Stark GR . 1996 Mol Cell Biol 16: 369–375

  • Mashberg A . 1993 J of NCI 85: 1525

  • Maxwell SA, Sack PG, Gutterman JU and Gallick GE . 1989 Cancer Res 49: 1130–1137

  • Moroni MC, Willingham MC and Beguinot L . 1992 J Biol Chem 267: 2714–2722

  • Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R and Yu H . 1999 Cancer Res 59: 5059–5063

  • Ozanne B, Richards CS and Hendler F . 1986 J Pathol 149: 9–14

  • Park OK, Schaefer TS and Nathans D . 1996 PNAS 93: 13704–13708

  • Partridge M, Green MR, Langdon JD and Feldman M . 1989 Br J Cancer 60: 542–548

  • Roberts AB and Sporn MB . 1985 Cancer Sur 4: 683–705

  • Rubin Grandis J, Zeng Q and Tweardy DJ . 1996a Nature Med 2: 237–240

  • Rubin Grandis J, Chakraborty A, Melhem MF, Zeng Q and Tweardy DJ . 1997 Oncogene 15: 409–416

  • Rubin Grandis J, Tweardy DJ and Melhem MF . 1998a Clin Cancer Res 4: 13–20

  • Rubin Grandis J, Chakraborty A, Zeng Q, Melhem MF and Tweardy DJ . 1998b J Cell Biochem 69: 55–62

  • Rubin Grandis J, Melhem MF, Gooding WE, Day R, Holst VA, Wagener MM, Drenning SD and Tweardy DJ . 1998c J NCI 90: 824–832

  • Rubin Grandis J, Drenning SD, Chakraborty A, Zhou Min-Yu, Zeng Q and Pitt AS . 1998d J Clin Invest 102: 1385–1392

  • Rubin Grandis J, Drenning SD, Zeng Q, Watkins SC, Melhem MF, Endo S, Johnson DE, Huang L and Kim JD . 1999 Proc Natl Acad Sci USA in press

  • Sadowski HB, Shuai K, Darnell JE and Gilman MZ . 1993 Science 261: 1739

  • Sartor CI, Dziubinski ML Yu CL, Jove R and Ethier SP . 1997 Cancer Res 57: 978–987

  • Seidel HM, Milocco LH, Lamb P, Darnell JE, Stein RB and Rosen J . 1995 Proc Natl Acad Sci USA 92: 3041–3045

  • Sharif M, Saskawa N and Hanley MR . 1994 Mol Cell Endocrin 100: 115–119

  • Siegfried JM, DeMichele MA, Hunt JD, Davis AG, Vohra KP and Pilewski JM . 1997 Am J Resp Crit Care Med 156: 358–366

  • Siegfried JM, Guentert PJ and Gaither AL . 1993 Anatomical Record 236: 241–247

  • Slaughter DA . 1946 Surgery 20: 133–138

  • Todd R, Donoff BR and Gertz R . 1989 Carcinogenesis 10: 1553–1556

  • Ulrich A and Schlessinger J . 1990 Cell 61: 203–212

  • US Department of Health and Human Services . 1991 Cancers of the Oral Cavity and Pharynx A Statistics Review Monograph, 1973–1987

  • Vogelstein B and Kinzler KW . 1993 Trends in Genetics 9: 138–141

  • Watson CJ and Miller WR . 1995 Br J Cancer 71: 840–844

  • Weichselbaum RR, Dunphy EJ, Beckett MA, Tybor AG, Moran WJ, Goldman ME, Vokes EE and Panje WR . 1989 Head Neck 11: 437–442

  • Wegenka UM, Buschmann J, Lutticken C, Heinrich PC and Horn F . 1993 Mol Cell Biol 13: 276–288

  • Yamamoto T, Katama N, Kawano H, Shimizu S, Kuroki T, Toyoshima K, Rikimaru K, Nomura N, Ishizaki R, Pastan I, Gamou S and Shimizu N . 1986 Cancer Res 46: 414–416

  • Yoshida K, Kyo E, Tsuda T, Tsujino T, Ito M and Tahara E . 1990 Int J Cancer 45: 131–135

  • Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J and Jove R . 1995 Science 269: 81

  • Zhong Z, Wen Z and Darnell JE . 1994 Science 264: 95–98

  • Zushi S, Shinomura Y, Kiyohara T, Miyazaki Y, Kondo S, Sugimachi M, Higashimoto Y, Kanayama S and Matsuzawa Y . 1998 Int J Cancer 78: 326–330

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Authors and Affiliations

  1. Department of Otolaryngology, University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, 15213, Pennsylvania, PA, USA

    John I Song & Jennifer Rubin Grandis

  2. Department of Pharmacology, University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, 15213, Pennsylvania, PA, USA

    Jennifer Rubin Grandis

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  1. John I Song
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Song, J., Grandis, J. STAT signaling in head and neck cancer. Oncogene 19, 2489–2495 (2000). https://doi.org/10.1038/sj.onc.1203483

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