title: KIF20A-mediated RNA granule transport system promotes the invasiveness of pancreatic cancer cells.
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 the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.
authors.affiliation: Department of Endoscopic Diagnostics and Therapeutics, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. Electronic address: ktaniuchi@kochi-u.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.affiliation: Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016547:Kinesins / Q000502:physiology*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics
chemical_list: D000089982:ADP-Ribosylation Factor 6; C576602:ARHGEF4 protein, human; C498780:IGF2BP3 protein, human; C410089:KIF20A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D016547:Kinesins; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human