title: IGF2BP3-mediated translation in cell protrusions promotes cell invasiveness and metastasis of pancreatic cancer.
abstract: Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that IGF2BP3 promoted the invasiveness and metastasis of pancreatic cancers through locally translated IGF2BP3-bound transcripts. In neural cells, transcripts sorted into cytoplasmic RNA granules are transported to dendrites and translated in these dendrites, thereby mediating long-term synaptic plasticity; however, such cytoplasmic RNA granules are not known to contribute to the progression of pancreatic cancer. We show evidence that IGF2BP3 and IGF2BP3-bound transcripts are localized in cytoplasmic RNA granules that accumulate in membrane protrusions of pancreatic cancer cells. Specific IGF2BP3-bound transcripts-ARF6 and ARHGEF4-that are preferentially translated in membrane protrusions induce further formation of membrane protrusions; consequently, IGF2BP3 promotes cell invasiveness and tumor metastasis. Our results provide insight into the link between regulation of localized translation in cell protrusions and the invasiveness and metastasis of pancreatic cancers. New therapies that prevent local translation in cell protrusions may hold significant clinical promise.
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi , Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.affiliation: Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Kochi , Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi , Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hanazaki
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi , Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D064593:Heterografts; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C498780:IGF2BP3 protein, human; D016601:RNA-Binding Proteins