PMID- 24190430
OWN - NLM
STAT- MEDLINE
DCOM- 20140121
LR  - 20211021
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 210
IP  - 12
DP  - 2013 Nov 18
TI  - Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone 
      via RXRgamma activation.
PG  - 2675-92
LID - 10.1084/jem.20122292 [doi]
AB  - Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with 
      poor prognosis in patients with colon cancer. Here, we found that spironolactone 
      (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can 
      up-regulate NKG2DL expression in multiple colon cancer cell lines by activating 
      the ATM-Chk2-mediated checkpoint pathway, which in turn enhances tumor 
      elimination by natural killer cells. SPIR can also up-regulate the expression of 
      metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell 
      invasiveness. Although SPIR is an aldosterone antagonist, its antitumor effects 
      are independent of the mineralocorticoid receptor pathway. By screening the human 
      nuclear hormone receptor siRNA library, we identified retinoid X receptor gamma 
      (RXRgamma) instead as being indispensable for the antitumor functions of SPIR. 
      Collectively, our results strongly support the use of SPIR or other RXRgamma agonists 
      with minimal side effects for colon cancer prevention and therapy.
FAU - Leung, Wai-Hang
AU  - Leung WH
AD  - Department of Bone Marrow Transplantation and Cellular Therapy; 2 Department of 
      Chemical Biology & Therapeutics; and 3 Department of Pathology, St. Jude 
      Children's Research Hospital, Memphis, Tennessee 38105.
FAU - Vong, Queenie P
AU  - Vong QP
FAU - Lin, Wenwei
AU  - Lin W
FAU - Janke, Laura
AU  - Janke L
FAU - Chen, Taosheng
AU  - Chen T
FAU - Leung, Wing
AU  - Leung W
LA  - eng
GR  - P30 CA021765/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131104
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (Ligands)
RN  - 0 (MHC class I-related chain A)
RN  - 0 (MICB antigen)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 0 (Retinoid X Receptor gamma)
RN  - 0 (TIMP2 protein, human)
RN  - 0 (TIMP3 protein, human)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-3)
RN  - 0 (ULBP1 protein, human)
RN  - 0 (ULBP2 protein, human)
RN  - 0 (ULBP3 protein, human)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 27O7W4T232 (Spironolactone)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Colorectal Neoplasms/*drug therapy/*metabolism/secondary
MH  - Cytotoxicity, Immunologic/drug effects
MH  - GPI-Linked Proteins/genetics/metabolism
MH  - Histocompatibility Antigens Class I/genetics/metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Killer Cells, Natural/drug effects/immunology
MH  - Ligands
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - NK Cell Lectin-Like Receptor Subfamily K/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Neoplasm/genetics/metabolism
MH  - Receptors, Mineralocorticoid/metabolism
MH  - Retinoid X Receptor gamma/*agonists/antagonists & inhibitors/genetics
MH  - Signal Transduction
MH  - Spironolactone/*pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics
MH  - Tissue Inhibitor of Metalloproteinase-3/genetics
MH  - Up-Regulation/drug effects
MH  - Xenograft Model Antitumor Assays
PMC - PMC3832934
EDAT- 2013/11/06 06:00
MHDA- 2014/01/22 06:00
PMCR- 2014/05/18
CRDT- 2013/11/06 06:00
PHST- 2013/11/06 06:00 [entrez]
PHST- 2013/11/06 06:00 [pubmed]
PHST- 2014/01/22 06:00 [medline]
PHST- 2014/05/18 00:00 [pmc-release]
AID - jem.20122292 [pii]
AID - 20122292 [pii]
AID - 10.1084/jem.20122292 [doi]
PST - ppublish
SO  - J Exp Med. 2013 Nov 18;210(12):2675-92. doi: 10.1084/jem.20122292. Epub 2013 Nov 
      4.