title: ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis.
abstract: 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.
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iriyama
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Takeda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Junya
authors.initials: J
authors.lastname: Mizukami
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Umeda
authors.forename: Takuya
authors.initials: T
authors.lastname: Noguchi
authors.forename: Isao
authors.initials: I
authors.lastname: Naguro
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishitoh
authors.forename: Kaoru
authors.initials: K
authors.lastname: Saegusa
authors.forename: Kei
authors.initials: K
authors.lastname: Tobiume
authors.forename: Toshiki
authors.initials: T
authors.lastname: Homma
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Aiko
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chida
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kamei
authors.forename: Shiro
authors.initials: S
authors.lastname: Kozuma
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsuzawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000201:enzymology; D015603:Keratinocytes / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000276:immunology; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; C116394:MAP kinase kinase kinase 6