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

• Published in: Oncogene Vol. 23; no. 28; pp. 4921 - 4929
• Main Authors: KANDA, Naoki, SENO, Hiroshi, SEKIKAWA, Akira, KAWADA, Mayumi, SUZUKI, Katsumasa, KAYAHARA, Takahisa, FUKUI, Hirokazu, SAWADA, Mitsutaka, CHIBA, Tsutomu, KONDA, Yoshitaka, MARUSAWA, Hiroyuki, KANAI, Masashi, NAKAJIMA, Toshio, KAWASHIMA, Tomoko, NANAKIN, Apichart, SAWABU, Tateo, UENOYAMA, Yoshito
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 17.06.2004; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; Acute-Phase Proteins - genetics; Acute-Phase Proteins - metabolism; AKT protein; Antibodies; Apoptosis; Biological and medical sciences; Cell Division; Cell growth; Cell Line, Tumor; Cell Nucleus - genetics; Cell physiology; Cell survival; Cell Survival - physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic - genetics; Humans; Inhibitor of Apoptosis Proteins; Janus; Janus kinase; Kinases; Kinetics; Medical sciences; Microtubule-Associated Proteins - genetics; Molecular and cellular biology; Neoplasm Proteins; Proteins; Signal Transduction; Stat3 protein; STAT3 Transcription Factor; Stomach Neoplasms; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survivin; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription; Tumorigenesis; Tumors; survivin; Association; STAT3; Digestive diseases; cancer; stomach; Malignant tumor; Gene expression; Carcinogenesis; Survival; Stomach cancer; Gastric disease
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207606

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.2004