Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer.
Abnormalities in signal transducer and activator of transcription (STAT) signaling, especially STAT3 and STAT5, are involved in the oncogenesis of several human cancers, including gastric cancer (GC). However, the downstream targets of STAT3 and STAT5 are not fully identified, and the precise roles and the prognostic value of STAT3 and STAT5 in GC have not been fully characterized. In this study, we used ChIP-on-chip to identify STAT3 and STAT5 target genes on a whole genome scale in AGS cells, a human GC cell line. A total of 2,514 and 1,314 genes were identified as STAT3 and STAT5 target genes, which were mainly related to cell growth, metabolism, differentiation, adhesion, immune response, and stress response. Furthermore, we depleted STAT3 and STAT5 with a small interfering RNA, respectively. Our results demonstrate that STAT3, but not STAT5, is involved in GC cell growth and cell cycle progression through regulation of gene expression, such as Bcl-2, p16(ink4a) and p21(waf1/cip1). Moreover, expression of pSTAT3(Tyr705) correlates with TNM stage, differentiation and survival, and is a significant prognostic factor in GC. Therefore, our findings provide novel evidence that STAT3 may be a potential therapeutic target for GC treatment and pSTAT3(Tyr705) expression can predict prognosis in GC.
GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Shanghai, China.
Hua
H
Xiong
Wan
W
Du
Ji-Lin
JL
Wang
Ying-Chao
YC
Wang
Jie-Ting
JT
Tang
Jie
J
Hong
Jing-Yuan
JY
Fang
D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor