title: Critical role of XBP1 in cancer signalling is regulated by PIN1.
abstract: XBP1 (X-box-binding protein 1) is activated in cancer and has a pivotal role in tumorigenesis and progression of human cancer. In particular, the XBP1 transcriptional regulatory network is well known to drive cancer development, but little is known about whether the stability of XBP1 is regulated and, if so, what controls the stability of XBP1. In the present study we show that PIN1 prolyl isomerase interacts with the active form of XBP1 (XBP1s) in a phosphorylation-dependent manner and promotes XBP1s-induced cell proliferation and transformation through the regulation of XBP1 stability. By contrast, depletion of Pin1 in cancer cells reduced XBP1s expression, which subsequently inhibits cell proliferation and transformation. Interestingly, XBP1s activates multiple oncogenic pathways including NF-κB (nuclear factor κB), AP1 (activator protein 1) and Myc, and down-regulates PIN1 transcription via a negative-feedback mechanism through p53 induction. Ultimately, reciprocal regulation of Pin1 and XBP1s is associated with the activation of oncogenic pathways, and the relationship of PIN1 and XBP1 may be an attractive target for novel therapy in cancers.
authors.affiliation: School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Unbin
authors.initials: U
authors.lastname: Chae
authors.affiliation: School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea Renal Division, School of Medicine, Washington University in St Louis, St. Louis, MO 63130, U.S.A.
authors.forename: Sun-Ji
authors.initials: SJ
authors.lastname: Park
authors.affiliation: School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA 02115, U.S.A.
authors.forename: Shou
authors.initials: S
authors.lastname: Wei
authors.affiliation: School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
authors.forename: Ju-Sik
authors.initials: JS
authors.lastname: Min
authors.affiliation: School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea New Drug Development Center, DGMIF, Daegu, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, U.S.A.
authors.forename: Ann-Hwee
authors.initials: AH
authors.lastname: Lee
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA 02115, U.S.A.
authors.forename: Kun Ping
authors.initials: KP
authors.lastname: Lu
authors.affiliation: School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea shmin03@dgmif.re.k lee1@knu.ac.kr.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.affiliation: New Drug Development Center, DGMIF, Daegu, Republic of Korea shmin03@dgmif.re.k lee1@knu.ac.kr.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Min
mesh_terms: D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction; D000071717:X-Box Binding Protein 1 / Q000378:metabolism*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000606846:PIN1 protein, human
keywords: PIN1; XBP1; cancer; isomerase