Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B
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Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B. / Skov, Søren; Pedersen, Marianne Terndrup; Andresen, Lars; Straten, Per Thor; Woetmann, Anders; Odum, Niels.
I: Cancer Research, Bind 65, Nr. 23, 2005, s. 11136-45.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B
AU - Skov, Søren
AU - Pedersen, Marianne Terndrup
AU - Andresen, Lars
AU - Straten, Per Thor
AU - Woetmann, Anders
AU - Odum, Niels
N1 - Keywords: Antibiotics, Antineoplastic; Apoptosis; Cell Line, Tumor; Depsipeptides; Enzyme Inhibitors; Glycogen Synthase Kinase 3; Histocompatibility Antigens Class I; Histone Deacetylases; Humans; Jurkat Cells; Killer Cells, Natural; Neoplasms; T-Lymphocytes
PY - 2005
Y1 - 2005
N2 - We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3 by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T cells, and CD8 T cells.
AB - We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3 by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T cells, and CD8 T cells.
U2 - 10.1158/0008-5472.CAN-05-0599
DO - 10.1158/0008-5472.CAN-05-0599
M3 - Journal article
C2 - 16322264
VL - 65
SP - 11136
EP - 11145
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 23
ER -
ID: 10615235