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Inhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathway

dc.contributor.authorDu, Wanen_US
dc.contributor.authorHong, Jieen_US
dc.contributor.authorWang, Ying‐chaoen_US
dc.contributor.authorZhang, Yan‐jieen_US
dc.contributor.authorWang, Pingen_US
dc.contributor.authorSu, Wen‐yuen_US
dc.contributor.authorLin, Yan‐weien_US
dc.contributor.authorLu, Rongen_US
dc.contributor.authorZou, Wei‐pingen_US
dc.contributor.authorXiong, Huaen_US
dc.contributor.authorFang, Jing‐yuanen_US
dc.date.accessioned2012-08-09T14:55:42Z
dc.date.available2013-10-01T17:06:31Zen_US
dc.date.issued2012-08en_US
dc.identifier.citationDu, Wan; Hong, Jie; Wang, Ying‐chao ; Zhang, Yan‐jie ; Wang, Ping; Su, Wen‐yu ; Lin, Yan‐wei ; Lu, Rong; Zou, Wei‐ping ; Xiong, Hua; Fang, Jing‐yuan (2012). "Inhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathway." Journal of Cellular and Molecular Medicine (8): 1878-1888. <http://hdl.handle.net/2027.42/92399>en_US
dc.identifier.issn1582-1838en_US
dc.identifier.issn1582-4934en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/92399
dc.description.abstractAbnormalities in the JAK2/STAT3 pathway are involved in the pathogenesis of colorectal cancer (CRC), including apoptosis. However, the exact mechanism by which dysregulated JAK2/STAT3 signalling contributes to the apoptosis has not been clarified. To investigate the role of both JAK2 and STAT3 in the mechanism underlying CRC apoptosis, we inhibited JAK2 with AG490 and depleted STAT3 with a small interfering RNA. Our data showed that inhibition of JAK2/STAT3 signalling induced CRC cellular apoptosis via modulating the Bcl‐2 gene family, promoting the loss of mitochondrial transmembrane potential (Δψm) and the increase of reactive oxygen species. In addition, our results demonstrated that the translocation of cytochrome c (Cyt c), caspase activation and cleavage of poly (ADP‐ribose) polymerase (PARP) were present in apoptotic CRC cells after down‐regulation of JAK2/STAT3 signalling. Moreover, inhibition of JAK2/STAT3 signalling suppressed CRC xenograft tumour growth. We found that JAK2/STAT3 target genes were decreased; meanwhile caspase cascade was activated in xenograft tumours. Our findings illustrated the biological significance of JAK2/STAT3 signalling in CRC apoptosis, and provided novel evidence that inhibition of JAK2/STAT3 induced apoptosis via the mitochondrial apoptotic pathway. Therefore, JAK2/STAT3 signalling may be a potential target for therapy of CRC.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.publisherBlackwell Publishing Ltden_US
dc.subject.otherMitochondrial Apoptotic Pathwayen_US
dc.subject.otherApoptosisen_US
dc.subject.otherJAK2/STAT3en_US
dc.subject.otherColorectal Canceren_US
dc.titleInhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathwayen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Surgery, University of Michigan, Ann Arbor, MI, USAen_US
dc.contributor.affiliationotherGI Division, Shanghai Jiao‐Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao‐Tong University); State Key Laboratory of Oncogene and Related Genes, Shanghai, Chinaen_US
dc.identifier.pmid22050790en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/92399/1/jcmm1483.pdf
dc.identifier.doi10.1111/j.1582-4934.2011.01483.xen_US
dc.identifier.sourceJournal of Cellular and Molecular Medicineen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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