PMID- 27013197
OWN - NLM
STAT- MEDLINE
DCOM- 20170728
LR  - 20180418
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 76
IP  - 11
DP  - 2016 Jun 1
TI  - NFAT1 Directly Regulates IL8 and MMP3 to Promote Melanoma Tumor Growth and
      Metastasis.
PG  - 3145-55
LID - 10.1158/0008-5472.CAN-15-2511 [doi]
AB  - Nuclear factor of activated T cell (NFAT1, NFATC2) is a transcription factor that
      binds and positively regulates IL2 expression during T-cell activation. NFAT1 has
      important roles in both innate and adaptive immune responses, but its involvement
      in cancer is not completely understood. We previously demonstrated that NFAT1
      contributes to melanoma growth and metastasis by regulating the autotaxin gene
      (Enpp2). Here, we report a strong correlation between NFAT1 expression and
      metastatic potential in melanoma cell lines and tumor specimens. To elucidate the
      mechanisms underlying NFAT1 overexpression during melanoma progression, we
      conducted a microarray on a highly metastatic melanoma cell line in which NFAT1
      expression was stably silenced. We identified and validated two downstream
      targets of NFAT1, IL8, and MMP3. Accordingly, NFAT1 depletion in metastatic
      melanoma cell lines was associated with reduced IL8 and MMP3 expression, whereas 
      NFAT1 overexpression in a weakly metastatic cell line induced expression of these
      targets. Restoration of NFAT1 expression recovered IL8 and MMP3 expression levels
      back to baseline, indicating that both are direct targets of NFAT1. Moreover, in 
      vivo studies demonstrated that NFAT1 and MMP3 promoted melanoma tumor growth and 
      lung metastasis. Collectively, our findings assign a new role for NFAT1 in
      melanoma progression, underscoring the multifaceted functions that
      immunomodulatory factors may acquire in an unpredictable tumor microenvironment. 
      Cancer Res; 76(11); 3145-55. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Shoshan, Einav
AU  - Shoshan E
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Braeuer, Russell R
AU  - Braeuer RR
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Kamiya, Takafumi
AU  - Kamiya T
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Mobley, Aaron K
AU  - Mobley AK
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Huang, Li
AU  - Huang L
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Vasquez, Mayra E
AU  - Vasquez ME
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Velazquez-Torres, Guermarie
AU  - Velazquez-Torres G
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Chakravarti, Nitin
AU  - Chakravarti N
AD  - Department of Pathology, The University of Texas MD Anderson Cancer Center,
      Houston, Texas.
FAU - Ivan, Cristina
AU  - Ivan C
AD  - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer
      Center, Houston, Texas.
FAU - Prieto, Victor
AU  - Prieto V
AD  - Department of Pathology, The University of Texas MD Anderson Cancer Center,
      Houston, Texas.
FAU - Villares, Gabriel J
AU  - Villares GJ
AD  - Department of Biology, University of St. Thomas, Houston, Texas.
FAU - Bar-Eli, Menashe
AU  - Bar-Eli M
AD  - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas. mbareli@mdanderson.org.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P50 CA093459/CA/NCI NIH HHS/United States
GR  - R01 CA076098/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160324
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (IL8 protein, human)
RN  - 0 (Interleukin-8)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (NFATC2 protein, human)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - Female
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Interleukin-8/genetics/*metabolism
MH  - Lung Neoplasms/genetics/metabolism/*secondary
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Melanoma/genetics/metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - NFATC Transcription Factors/genetics/*metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Prognosis
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Rate
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
PMC - PMC4891299
MID - NIHMS775770
EDAT- 2016/03/26 06:00
MHDA- 2017/07/29 06:00
CRDT- 2016/03/26 06:00
PHST- 2015/09/14 00:00 [received]
PHST- 2016/03/21 00:00 [accepted]
PHST- 2016/03/26 06:00 [entrez]
PHST- 2016/03/26 06:00 [pubmed]
PHST- 2017/07/29 06:00 [medline]
AID - 0008-5472.CAN-15-2511 [pii]
AID - 10.1158/0008-5472.CAN-15-2511 [doi]
PST - ppublish
SO  - Cancer Res. 2016 Jun 1;76(11):3145-55. doi: 10.1158/0008-5472.CAN-15-2511. Epub
      2016 Mar 24.