title: KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro.
abstract: Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer.
authors.affiliation: Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere, Finland; Fimlab Laboratories, Biokatu 4, 33520 Tampere, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Laurila
authors.affiliation: Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere, Finland; Fimlab Laboratories, Biokatu 4, 33520 Tampere, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Vuorinen
authors.affiliation: Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Savinainen
authors.affiliation: Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rauhala
authors.affiliation: Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere, Finland; Fimlab Laboratories, Biokatu 4, 33520 Tampere, Finland. Electronic address: anne.kallioniemi@uta.fi.
authors.forename: Anne
authors.initials: A
authors.lastname: Kallioniemi
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D014407:Tumor Cells, Cultured; D028901:alpha Karyopherins / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C587929:KPNA7 protein, human; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D028901:alpha Karyopherins
keywords: Autophagy; Cell cycle; KPNA7; Nuclear transport; Pancreatic cancer; p21