PMID- 27317874
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20171028
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 380
IP  - 1
DP  - 2016 Sep 28
TI  - RUNX2 promotes breast cancer bone metastasis by increasing integrin
      alpha5-mediated colonization.
PG  - 78-86
LID - 10.1016/j.canlet.2016.06.007 [doi]
LID - S0304-3835(16)30367-6 [pii]
AB  - Runt-related transcription factor 2 (RUNX2) is regarded as an important
      contributor to breast cancer bone metastasis. However, previous studies did not
      provide direct clinical evidence for a role of RUNX2 in bone-specific metastasis 
      in breast cancer, and the mechanism of RUNX2 in cancer cell recruitment and
      adhesion to the bone remains unclear. In this study, we showed that RUNX2
      expression is positively correlated with the risk of bone-specific metastasis in 
      lymph node-negative breast cancer patients. Then, we identified ITGA5 as a
      transcriptional target of RUNX2 from multiple candidate genes encoding adhesion
      molecules or chemokine receptors. We further provided experimental and clinical
      evidence that RUNX2, in an integrin alpha5-dependent manner, promotes the
      attraction and adhesion of breast cancer cells to the bone and confers cancer
      cell survival and bone colonization advantages. Overall, our findings clarify an 
      adhesion-dependent mechanism of RUNX2 for the osteotropism and bone colonization 
      of breast cancer cells and implicate RUNX2 and integrin alpha5 as potential
      molecular markers for the prediction of bone metastasis and therapeutic targets
      for the treatment of breast cancer bone metastasis.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Li, Xiao-Qing
AU  - Li XQ
AD  - Department of Biochemistry and Molecular Biology, Tianjin Medical University
      Cancer Institute and Hospital, National Clinical Research Center of Cancer,
      Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Treatment
      of the Ministry of Education, Tianjin Medical University Cancer Institute and
      Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
FAU - Lu, Jun-Tao
AU  - Lu JT
AD  - Department of Biochemistry and Molecular Biology, Tianjin Medical University
      Cancer Institute and Hospital, National Clinical Research Center of Cancer,
      Tianjin 300060, China.
FAU - Tan, Cong-Cong
AU  - Tan CC
AD  - Department of Biochemistry and Molecular Biology, Tianjin Medical University
      Cancer Institute and Hospital, National Clinical Research Center of Cancer,
      Tianjin 300060, China.
FAU - Wang, Qing-Shan
AU  - Wang QS
AD  - Department of Biochemistry and Molecular Biology, Tianjin Medical University
      Cancer Institute and Hospital, National Clinical Research Center of Cancer,
      Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Treatment
      of the Ministry of Education, Tianjin Medical University Cancer Institute and
      Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
FAU - Feng, Yu-Mei
AU  - Feng YM
AD  - Department of Biochemistry and Molecular Biology, Tianjin Medical University
      Cancer Institute and Hospital, National Clinical Research Center of Cancer,
      Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Treatment
      of the Ministry of Education, Tianjin Medical University Cancer Institute and
      Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
      Electronic address: ymfeng@tmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160616
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Integrin alpha5)
RN  - 0 (RUNX2 protein, human)
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/genetics/*metabolism/*secondary
MH  - Breast Neoplasms/genetics/*metabolism/*secondary/therapy
MH  - Cell Adhesion
MH  - Cell Line, Tumor
MH  - *Cell Movement
MH  - Cell Proliferation
MH  - Coculture Techniques
MH  - Core Binding Factor Alpha 1 Subunit/genetics/*metabolism
MH  - Disease-Free Survival
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Integrin alpha5/genetics/*metabolism
MH  - Kaplan-Meier Estimate
MH  - Mice
MH  - Osteoblasts/*metabolism/pathology
MH  - RNA Interference
MH  - Signal Transduction
MH  - Time Factors
MH  - Transcription, Genetic
MH  - Transfection
OTO - NOTNLM
OT  - *Bone metastasis
OT  - *Breast cancer
OT  - *Integrin alpha5
OT  - *RUNX2
EDAT- 2016/06/19 06:00
MHDA- 2017/07/27 06:00
CRDT- 2016/06/19 06:00
PHST- 2015/12/10 00:00 [received]
PHST- 2016/04/01 00:00 [revised]
PHST- 2016/06/07 00:00 [accepted]
PHST- 2016/06/19 06:00 [entrez]
PHST- 2016/06/19 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
AID - S0304-3835(16)30367-6 [pii]
AID - 10.1016/j.canlet.2016.06.007 [doi]
PST - ppublish
SO  - Cancer Lett. 2016 Sep 28;380(1):78-86. doi: 10.1016/j.canlet.2016.06.007. Epub
      2016 Jun 16.