title: EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1.
abstract: Dysregulation of the EGFR signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential. In this study, we demonstrated a role for EGFR translocation in regulating transcription of miR-1-1, which directly targets expression of TWIST1. Consistent with these findings, we observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human prostate cancer specimens and additional datasets. Our findings support a model in which nuclear EGFR acts as a transcriptional repressor to constrain the tumor-suppressive role of miR-1 and sustain oncogenic activation of TWIST1, thereby leading to accelerated bone metastasis.
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Sheng
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Cell and Cancer Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Yin
authors.affiliation: Cell and Cancer Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Heather
authors.initials: H
authors.lastname: Sheppard-Tillman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California.
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. liuy@tmu.edu.tw.
authors.forename: Yen-Nien
authors.initials: YN
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D020871:RNA Stability; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D066246:ErbB Receptors