title: Negative correlation of ITCH E3 ubiquitin ligase and miRNA-106b dictates metastatic progression in pancreatic cancer.
abstract: Pancreatic cancer is one of the major malignancies and cause for mortality across the world, with recurrence and metastatic progression remaining the single largest cause of pancreatic cancer mortality. Hence it is imperative to develop novel biomarkers of pancreatic cancer prognosis. The E3 ubiquitin ligase ITCH has been previously reported to inhibit the tumor suppressive Hippo signaling by suppressing LATS1/2 in breast cancer and chronic lymphocytic leukemia. However, the role of ITCH in pancreatic cancer progression has not been described. Here we report that ITCH transcript and protein expression mimic metastatic trait in pancreatic cancer patients and cell lines. Loss-of-function studies of ITCH showed that the gene product is responsible for inducing metastasis in vivo. We furthermore show that hsa-miR-106b, which itself is down regulated in metastatic pancreatic cancer, directly interacts and inhibit ITCH expression. ITCH and hsa-miR-106b are thus potential biomarkers for pancreatic cancer prognosis.
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Zhu-Lin
authors.initials: ZL
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Luo
authors.affiliation: Chengdu Military Institute for Drug and Instrument Control, Chengdu, Sichuan 610020, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Dai
authors.affiliation: Medical Central Laboratory, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Fu-Zhou
authors.initials: FZ
authors.lastname: Tian
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Tang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases
keywords: ITCH; YAP; metastasis; miR-106b; pancreatic cancer