Absence of STAT1 disturbs the anticancer effect induced by STAT3 inhibition in head and neck carcinoma cell lines

The family of signal transducers and activators of transcription (STAT) are transcription factors. Among them, STAT I is associated with an apoptosis pathway, while STAT3 is associated with tumorigenicity in various cancer cells. In order to investigate the primary roles of STAT I and STAT3 in head and neck squamous cell carcinoma (HNSCC), we blocked STAT3 with two JAK inhibitors: AG490 (JAK2-STAT3 pathway inhibitor) and JAK total inhibitor. When we inhibited STAT3 with AG490, significant cell death was observed. However, in the case of JAK kinase total inhibitor, no cell growth retardation was observed. We focused on the role of STAT1 in this phenomenon. Suppression of STAT1 by si-RNA resulted in increased cell survival. Furthermore, the growth inhibitory effect of AG490 was reduced by treatment with si-RNA of STAT1. These results reveal that STAT1 is required to promote the tumor killing effect of STAT3 inhibition in HNSCC.Lui VWY, 2007, MOL PHARMACOL, V71, P1435, DOI 10.1124/mol.106.032284Yu H, 2004, NAT REV CANCER, V4, P97, DOI 10.1038/nrc1275Mora LB, 2002, CANCER RES, V62, P6659Janjua S, 2002, CELL DEATH DIFFER, V9, P1140, DOI 10.1038/sj.cdd.4401082Levy DE, 2002, NAT REV MOL CELL BIO, V3, P651, DOI 10.1038/nrm909Huang SY, 2002, ONCOGENE, V21, P2504, DOI 10.1038/sj/onc/1205341Shen YH, 2001, P NATL ACAD SCI USA, V98, P1543Sinibaldi D, 2000, ONCOGENE, V19, P5419Song JI, 2000, ONCOGENE, V19, P2489Decker T, 2000, ONCOGENE, V19, P2628Ramana CV, 2000, ONCOGENE, V19, P2619Ouchi T, 2000, P NATL ACAD SCI USA, V97, P5208Grandis JR, 2000, LARYNGOSCOPE, V110, P868Grandis JR, 2000, P NATL ACAD SCI USA, V97, P4227Schaefer LK, 1999, BIOCHEM BIOPH RES CO, V266, P481Turkson J, 1999, MOL CELL BIOL, V19, P7519Lim CP, 1999, J BIOL CHEM, V274, P31055Bromberg JF, 1999, CELL, V98, P295Gollob JA, 1999, J IMMUNOL, V162, P4472Grandis JR, 1998, J CLIN INVEST, V102, P1385Bromberg JF, 1998, MOL CELL BIOL, V18, P2553Kumar A, 1997, SCIENCE, V278, P1630Chung JK, 1997, MOL CELL BIOL, V17, P6508Zhu XJ, 1997, MOL CELL BIOL, V17, P6618Wen ZL, 1997, NUCLEIC ACIDS RES, V25, P2062DAVID M, 1995, SCIENCE, V269, P1721WEN ZL, 1995, CELL, V82, P241