title: Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells.
abstract: The heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by coordinating the translation of selected transcripts associated with proliferation and survival. hnRNP A18 binds to and stabilizes the transcripts of pro-survival genes harboring its RNA signature motif in their 3'UTRs. hnRNP A18 binds to ATR, RPA, TRX, HIF-1α and several protein translation factor mRNAs on polysomes and increases de novo protein translation under cellular stress. Most importantly, down regulation of hnRNP A18 decreases proliferation, invasion and migration in addition to significantly reducing tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, tissue microarrays performed on human melanoma, prostate, breast and colon cancer indicate that hnRNP A18 is over expressed in 40 to 60% of these malignant tissue as compared to normal adjacent tissue. Immunohistochemistry data indicate that hnRNP A18 is over expressed in the stroma and hypoxic areas of human tumors. These data thus indicate that hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. hnRNP A18 therefore represents a new target to selectively inhibit protein translation in tumor cells.
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, School of Medicine, Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Chang
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, School of Medicine, Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA.
authors.forename: Palak R
authors.initials: PR
authors.lastname: Parekh
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, School of Medicine, Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, School of Medicine, Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA.
authors.forename: Duc M
authors.initials: DM
authors.lastname: Nguyen
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, School of Medicine, Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA.
authors.forename: France
authors.initials: F
authors.lastname: Carrier
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D014176:Protein Biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D051716:Replication Protein A / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C491390:CIRBP protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C497167:RPA1 protein, human; D051716:Replication Protein A; C491203:TXN protein, human; D013879:Thioredoxins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: RNA-binding protein; cancer; hnRNP A18; hypoxia; protein translation
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