PMID- 29212252
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240318
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 55
DP  - 2017 Nov 7
TI  - C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3 
      signaling axis in breast cancer cells.
PG  - 94591-94605
LID - 10.18632/oncotarget.21813 [doi]
AB  - The CC motif chemokine receptor 1 (CCR1) has been implicated in tumor invasion 
      and metastasis in numerous cancers. However, the detailed mechanism of CCR1 
      upregulation in metastatic tumor cells is poorly understood. The aim of this 
      study was to clarify the regulatory mechanism underlying transcriptional 
      activation of the CCR1 gene in response to epidermal growth factor (EGF) 
      stimulation in breast cancer cells. CCR1 was highly expressed in human breast 
      invasive ductal carcinoma (IDC) compared to adjacent normal tissues. Upon EGF 
      stimulation, CCR1 expression was upregulated at the transcriptional level. 
      Promoter analysis showed that signal transducer and activator of transcription 3 
      (STAT3) is necessary for EGF-induced CCR1 promoter activation, and STAT3 
      silencing abrogated EGF-induced CCR1 transcription. Pharmacological inhibition 
      and short hairpin RNA-mediated knockdown experiments showed that AKT-dependent 
      mammalian target of rapamycin (mTOR) activation was involved in the 
      phosphorylation of serine-727 of STAT3, which in turn stimulated the 
      transcription of the CCR1 gene. In conclusion, the AKT-mTOR-STAT3 signaling axis 
      contributes to EGF-induced CCR1 expression, which promotes invasion and 
      metastasis in breast cancer cells. We propose that the AKT-mTOR-STAT3 axis is a 
      potential therapeutic target for blocking the invasion and metastasis of breast 
      cancers.
FAU - Shin, Soon Young
AU  - Shin SY
AD  - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk 
      University, Seoul, Republic of Korea.
AD  - Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea.
FAU - Lee, Da Hyun
AU  - Lee DH
AD  - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk 
      University, Seoul, Republic of Korea.
FAU - Lee, Jishin
AU  - Lee J
AD  - Department of Pathology, Chonnam National University Medical School, Gwangju, 
      Republic of Korea.
FAU - Choi, Chan
AU  - Choi C
AD  - Department of Pathology, Chonnam National University Medical School, Gwangju, 
      Republic of Korea.
FAU - Kim, Ji-Young
AU  - Kim JY
AD  - Laboratory Animal Resource Center, Gwangju Institute of Science and Technology, 
      Gwangju, Republic of Korea.
FAU - Nam, Jeong-Seok
AU  - Nam JS
AD  - School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 
      Republic of Korea.
FAU - Lim, Yoongho
AU  - Lim Y
AD  - Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul, 
      Republic of Korea.
FAU - Lee, Young Han
AU  - Lee YH
AD  - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk 
      University, Seoul, Republic of Korea.
AD  - Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20171010
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5706898
OTO - NOTNLM
OT  - AKT
OT  - CCR1
OT  - STAT3
OT  - mTOR
OT  - metastasis
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2017/12/08 06:00
MHDA- 2017/12/08 06:01
PMCR- 2017/11/07
CRDT- 2017/12/08 06:00
PHST- 2017/06/08 00:00 [received]
PHST- 2017/09/20 00:00 [accepted]
PHST- 2017/12/08 06:00 [entrez]
PHST- 2017/12/08 06:00 [pubmed]
PHST- 2017/12/08 06:01 [medline]
PHST- 2017/11/07 00:00 [pmc-release]
AID - 21813 [pii]
AID - 10.18632/oncotarget.21813 [doi]
PST - epublish
SO  - Oncotarget. 2017 Oct 10;8(55):94591-94605. doi: 10.18632/oncotarget.21813. 
      eCollection 2017 Nov 7.