PMID- 28991374
OWN - NLM
STAT- MEDLINE
DCOM- 20180109
LR  - 20220318
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 244
IP  - 1
DP  - 2018 Jan
TI  - Synaptopodin-2 suppresses metastasis of triple-negative breast cancer via 
      inhibition of YAP/TAZ activity.
PG  - 71-83
LID - 10.1002/path.4995 [doi]
AB  - Triple-negative breast cancer (TNBC) represents the most aggressive subtype of 
      breast cancer, with a high incidence of distant metastasis; however, the 
      underlying mechanism for this frequent recurrence remains unclear. Herein, we 
      show that synaptopodin-2 (SYNPO2), a putative tumour suppressor in aggressive 
      cancer, is frequently downregulated in TNBC by methylation of the promoter of 
      SYNPO2. Low expression levels of SYNPO2 correlated significantly with 5-year 
      metastatic relapse, and predicted poorer prognosis in breast cancer patients. 
      Reintroduction of SYNPO2 inhibited the invasion and spontaneous metastasis of 
      TNBC cells in vivo. Strikingly, downregulation of SYNPO2 is essential for the 
      maintenance of stem cell-like properties in TNBC cells, leading to efficient 
      distant colonization and metastasis outgrowth. Moreover, we demonstrate that 
      SYNPO2 inhibits the activities of YAP and TAZ by stabilizing LATS2 protein, and 
      transduction of YAP-S127A abrogates the repressive role of SYNPO2 in metastasis. 
      Finally, immunohistochemical (IHC) analysis of breast cancer patient specimens 
      indicated that the SYNPO2-LATS2-YAP axis is clinically relevant. These findings 
      uncover a suppressive role of SYNPO2 in TNBC metastasis via inhibition of 
      YAP/TAZ, and suggest that SYNPO2 might provide a potential prognosis marker and 
      novel therapeutic strategy. Copyright (c) 2017 Pathological Society of Great 
      Britain and Ireland. Published by John Wiley & Sons, Ltd.
CI  - Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Liu, Junling
AU  - Liu J
AD  - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in 
      Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 
      PR China.
FAU - Ye, Liping
AU  - Ye L
AD  - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in 
      Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 
      PR China.
FAU - Li, Qingyuan
AU  - Li Q
AD  - Guangdong Country Garden School, Shunde, Foshan, Guangdong, PR China.
FAU - Wu, Xianqiu
AU  - Wu X
AD  - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in 
      Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 
      PR China.
FAU - Wang, Bin
AU  - Wang B
AD  - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in 
      Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 
      PR China.
FAU - Ouyang, Ying
AU  - Ouyang Y
AD  - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in 
      Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 
      PR China.
FAU - Yuan, Zhongyu
AU  - Yuan Z
AD  - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in 
      Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 
      PR China.
FAU - Li, Jun
AU  - Li J
AD  - Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, PR China.
FAU - Lin, Chuyong
AU  - Lin C
AUID- ORCID: 0000-0003-4887-5386
AD  - Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in 
      Southern China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 
      PR China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (SYNPO2 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (WWTR1 protein, human)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - EC 2.7.1.11 (LATS2 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - DNA Methylation
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Heterografts
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microfilament Proteins/genetics/*metabolism
MH  - Neoplasm Metastasis
MH  - Phosphoproteins/genetics/*metabolism
MH  - Prognosis
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Trans-Activators
MH  - Transcription Factors
MH  - Transcriptional Coactivator with PDZ-Binding Motif Proteins
MH  - Triple Negative Breast Neoplasms/metabolism/*pathology
MH  - Tumor Suppressor Proteins/genetics/metabolism
MH  - YAP-Signaling Proteins
OTO - NOTNLM
OT  - LATS2
OT  - SYNPO2
OT  - TAZ
OT  - TNBC
OT  - YAP
OT  - metastasis
OT  - stem cell-like properties
EDAT- 2017/10/11 06:00
MHDA- 2018/01/10 06:00
CRDT- 2017/10/10 06:00
PHST- 2017/03/22 00:00 [received]
PHST- 2017/09/27 00:00 [revised]
PHST- 2017/10/04 00:00 [accepted]
PHST- 2017/10/11 06:00 [pubmed]
PHST- 2018/01/10 06:00 [medline]
PHST- 2017/10/10 06:00 [entrez]
AID - 10.1002/path.4995 [doi]
PST - ppublish
SO  - J Pathol. 2018 Jan;244(1):71-83. doi: 10.1002/path.4995.