PMID- 28560452
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20191210
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 38
IP  - 1
DP  - 2017 Jul
TI  - Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to 
      reactivate protein phosphatase 2A.
PG  - 598-606
LID - 10.3892/or.2017.5667 [doi]
AB  - We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant 
      cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further 
      delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC 
      cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous 
      inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous 
      inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and 
      invasion of various cancer cells. PP2A is a tumor suppressor, which is 
      functionally defective in various cancers. Atn-induced metastasis inhibition was 
      associated with reactivation of PP2A, downregulation of CIP2A and Akt 
      phosphorylation. Silencing CIP2A enhanced Atn-induced metastasis inhibition and 
      apoptosis in TNBCs. Furthermore, ectopic expression of CIP2A or inhibition of 
      PP2A in TNBC cells abolished the effects of Atn. In conclusion, we found that 
      enhancement of PP2A activity by inhibition of CIP2A, at least in part, promotes 
      the anti-metastasis effect induced by Atn. Our findings disclose the novel 
      therapeutic mechanism of this targeted agent, and suggest the therapeutic 
      potential and feasibility of developing PP2A enhancers as a novel anticancer 
      strategy.
FAU - Huang, Qiuyue
AU  - Huang Q
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Qin, Shanshan
AU  - Qin S
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Yuan, Xiaoning
AU  - Yuan X
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Zhang, Liang
AU  - Zhang L
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Ji, Juanli
AU  - Ji J
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Liu, Xuewen
AU  - Liu X
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Ma, Wenjing
AU  - Ma W
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Zhang, Yunfei
AU  - Zhang Y
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Liu, Pengfei
AU  - Liu P
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Sun, Zhiting
AU  - Sun Z
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Zhang, Jingxuan
AU  - Zhang J
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Liu, Ying
AU  - Liu Y
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170524
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Autoantigens)
RN  - 0 (CIP2A protein, human)
RN  - 0 (Furans)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lignans)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.16 (PPP2CA protein, human)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - U76MR9VS6M (arctigenin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Apoptosis
MH  - Autoantigens/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Furans/*pharmacology/therapeutic use
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lignans/*pharmacology/therapeutic use
MH  - Membrane Proteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Phosphatase 2/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - Triple Negative Breast Neoplasms/*drug therapy/pathology
EDAT- 2017/06/01 06:00
MHDA- 2018/03/27 06:00
CRDT- 2017/06/01 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2017/05/15 00:00 [accepted]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/06/01 06:00 [entrez]
AID - 10.3892/or.2017.5667 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Jul;38(1):598-606. doi: 10.3892/or.2017.5667. Epub 2017 May 24.