A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS

被引：54

作者：

Amodeo, Valeria ^{[1
,2
]}

Deli, A. ^{[1
,2
]}

Betts, Joanne ^{[1
,2
]}

Bartesaghi, Stefano ^{[1
,2
]}

Zhang, Ying ^{[3
]}

Richard-Londt, Angela ^{[3
]}

Ellis, Matthew ^{[3
]}

Roshani, Rozita ^{[1
,2
]}

Vouri, Mikaella ^{[1
,2
]}

Galavotti, Sara ^{[1
,2
]}

Oberndorfer, Sarah ^{[1
,2
]}

Leite, Ana Paula ^{[1
,2
]}

Mackay, Alan ^{[4
]}

Lampada, Aikaterini ^{[1
,2
]}

Stratford, Eva Wessel ^{[5
]}

Li, Ningning ^{[3
]}

Dinsdale, David ^{[6
]}

Grimwade, David ^{[7
]}

Jones, Chris ^{[4
]}

Nicotera, Pierluigi ^{[8
]}

Michod, David ^{[1
,2
,9
]}

Brandner, Sebastian ^{[3
,10
]}

Salomoni, Paolo ^{[1
,2
,6
,11
]}

机构：

[1] UCL Canc Inst, London WC1E 6DD, England

[2] UCL Canc Inst, Samantha Dickson Brain Canc Unit, London WC1E 6DD, England

[3] UCL Inst Neurol, London WC1N 3BG, England

[4] Inst Canc Res, London SM2 5NG, England

[5] Norwegian Radium Hosp, N-0379 Oslo, Norway

[6] MRC, Toxicol Unit, Leicester LE1 7HB, Leics, England

[7] Kings Coll London, Guys Hosp, London SE1 9RT, England

[8] German Ctr Neurodegenerat Dis DZNE, D-53127 Bonn, Germany

[9] UCL Inst Child Hlth, London WC1N 1EH, England

[10] AstraZeneca R&D Gothenburg, Pepparedsleden 1, SE-43183 Molndal, Sweden

[11] DZNE, D-53127 Bonn, Germany

来源：

CELL REPORTS | 2017年 / 20卷 / 02期

关键词：

PML NUCLEAR-BODIES; NEURAL STEM-CELLS; ACUTE PROMYELOCYTIC LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; TUMOR-SUPPRESSOR PML; AXON GUIDANCE; SUBVENTRICULAR ZONE; NEURONAL MIGRATION; LAMINA INTERACTIONS; CEREBRAL-CORTEX;

D O I：

10.1016/j.celrep.2017.06.047

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/ stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells.

引用

页码：411 / 426

页数：16

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