ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis

Takayuki Iriyama, Kohsuke Takeda, Hiromi Nakamura, Yoshifumi Morimoto, Takumi Kuroiwa, Junya Mizukami, Tsuyoshi Umeda, Takuya Noguchi, Isao Naguro, Hideki Nishitoh, Kaoru Saegusa, Kei Tobiume, Toshiki Homma, Yutaka Shimada, Hitoshi Tsuda, Satoshi Aiko, Issei Imoto, Johji Inazawa, Kazuhiro Chida, Yoshimasa KameiShiro Kozuma, Yuji Taketani, Atsushi Matsuzawa, Hidenori Ichijo

研究成果: Article査読

106 被引用数 (Scopus)


Apoptosis and inflammation generally exert opposite effects on tumorigenesis: apoptosis serves as a barrier to tumour initiation, whereas inflammation promotes tumorigenesis. Although both events are induced by various common stressors, relatively little is known about the stress-induced signalling pathways regulating these events in tumorigenesis. Here, we show that stress-activated MAP3Ks, ASK1 and ASK2, which are involved in cellular responses to various stressors such as reactive oxygen species, differentially regulate the initiation and promotion of tumorigenesis. ASK2 in cooperation with ASK1 functioned as a tumour suppressor by exerting proapoptotic activity in epithelial cells, which was consistent with the reduction in ASK2 expression in human cancer cells and tissues. In contrast, ASK1-dependent cytokine production in inflammatory cells promoted tumorigenesis. Our findings suggest that ASK1 and ASK2 are critically involved in tumorigenesis by differentially regulating apoptosis and inflammation.

ジャーナルEMBO Journal
出版ステータスPublished - 2009 4月 8

ASJC Scopus subject areas

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)


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