Alterations of the nuclear transport system in hepatocellular carcinoma - New basis for therapeutic strategies

被引:25
作者
Beck, Martin [1 ]
Schirmacher, Peter [2 ]
Singer, Stephan [1 ,2 ]
机构
[1] European Mol Biol Lab, Heidelberg, Germany
[2] Univ Hosp Heidelberg, Inst Pathol, Heidelberg, Germany
关键词
Hepatocellular carcinoma; Nuclear transport; Nuclear pore complex; NF-KAPPA-B; MESSENGER-RNA EXPORT; APOPTOSIS SUSCEPTIBILITY GENE; EPITHELIAL OVARIAN-CARCINOMA; PORE COMPLEX COMPOSITION; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER CELLS; P53 TARGET GENES; LIVER-CANCER; BETA-CATENIN;
D O I
10.1016/j.jhep.2017.06.021
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Hepatocellular carcinoma (HCC) is among the most prevalent human malignancies worldwide with rising incidence in industrialised countries, few therapeutic options and poor prognosis. To expand and improve therapeutic strategies, identification of drug targets involved in several liver cancer-related pathways is crucial. Virtually all signal transduction cascades cross the nuclear envelope and therefore require components of the nuclear transport system (NTS), including nuclear transport receptors (e.g. importins and exportins) and the nuclear pore complex. Accordingly, members of the NTS represent promising targets for therapeutic intervention. Selective inhibitors of nuclear export have already entered clinical trials for various malignancies. Herein, we review the current knowledge regarding alterations of the NTS and their potential for targeted therapy in HCC. (C) 2017 Published by Elsevier B.V.
引用
收藏
页码:1051 / 1061
页数:11
相关论文
共 135 条
[1]   p21 in cancer: intricate networks and multiple activities [J].
Abbas, Tarek ;
Dutta, Anindya .
NATURE REVIEWS CANCER, 2009, 9 (06) :400-414
[2]   Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia [J].
Alexander, Thomas B. ;
Lacayo, Norman J. ;
Choi, John K. ;
Ribeiro, Raul C. ;
Pui, Ching-Hon ;
Rubnitz, Jeffrey E. .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (34) :4094-+
[3]   Selective inhibitors of nuclear export for the treatment of non-Hodgkin's lymphomas [J].
Azmi, Asfar S. ;
Al-Katib, Ayad ;
Aboukameel, Amro ;
McCauley, Dilara ;
Kauffman, Michael ;
Shacham, Sharon ;
Mohammad, Ramzi M. .
HAEMATOLOGICA, 2013, 98 (07) :1098-1106
[4]   The nuclear pore complex: understanding its function through structural insight [J].
Beck, Martin ;
Hurt, Ed .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2017, 18 (02) :73-89
[5]   Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain [J].
Begitt, A ;
Meyer, T ;
van Rossum, M ;
Vinkemeier, U .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (19) :10418-10423
[6]   Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets [J].
Boyault, Sandrine ;
Rickman, David S. ;
de Reynies, Aurelien ;
Balabaud, Charles ;
Rebouissou, Sandra ;
Jeannot, Emmanuelle ;
Herault, Aurelie ;
Saric, Jean ;
Belghiti, Jacques ;
Franco, Dominique ;
Bioulac-Sage, Paulette ;
Laurent-Puig, Pierre ;
Zucman-Rossi, Jessica .
HEPATOLOGY, 2007, 45 (01) :42-52
[7]   Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome [J].
Braun, Daniela A. ;
Sadowski, Carolin E. ;
Kohl, Stefan ;
Lovric, Svjetlana ;
Astrinidis, Susanne A. ;
Pabst, Werner L. ;
Gee, Heon Yung ;
Ashraf, Shazia ;
Lawson, Jennifer A. ;
Shril, Shirlee ;
Airik, Merlin ;
Tan, Weizhen ;
Schapiro, David ;
Rao, Jia ;
Choi, Won-Il ;
Hermle, Tobias ;
Kemper, Markus J. ;
Pohl, Martin ;
Ozaltin, Fatih ;
Konrad, Martin ;
Bogdanovic, Radovan ;
Buescher, Rainer ;
Helmchen, Udo ;
Serdaroglu, Erkin ;
Lifton, Richard P. ;
Antonin, Wolfram ;
Hildebrandt, Friedhelm .
NATURE GENETICS, 2016, 48 (04) :457-+
[8]   The human CAS (cellular apoptosis susceptibility) gene mapping on chromosome 20q13 is amplified in BT474 breast cancer cells and part of aberrant chromosomes in breast and colon cancer cell lines [J].
Brinkmann, U ;
Gallo, M ;
Polymeropoulos, MH ;
Pastan, I .
GENOME RESEARCH, 1996, 6 (03) :187-194
[9]   Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis [J].
Brinkmann, U ;
Brinkmann, E ;
Gallo, M ;
Scherf, U ;
Pastan, I .
BIOCHEMISTRY, 1996, 35 (21) :6891-6899
[10]   CLONING AND CHARACTERIZATION OF A CELLULAR APOPTOSIS SUSCEPTIBILITY GENE, THE HUMAN HOMOLOG TO THE YEAST CHROMOSOME SEGREGATION GENE CSE1 [J].
BRINKMANN, U ;
BRINKMANN, E ;
GALLO, M ;
PASTAN, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (22) :10427-10431