PMID- 36517864
OWN - NLM
STAT- MEDLINE
DCOM- 20230104
LR  - 20230131
IS  - 1757-2215 (Electronic)
IS  - 1757-2215 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Dec 14
TI  - ANGPTL4 functions as an oncogene through regulation of the ETV5/CDH5/AKT/MMP9 
      axis to promote angiogenesis in ovarian cancer.
PG  - 131
LID - 10.1186/s13048-022-01060-7 [doi]
LID - 131
AB  - BACKGROUND: Angiopoietin-like 4 (ANGPTL4) is highly expressed in a variety of 
      neoplasms and promotes cancer progression. Nevertheless, the mechanism of ANGPTL4 
      in ovarian cancer (OC) metastasis remains unclear. This study aimeds to explore 
      whether ANGPTL4 regulates OC progression and elucidate the underlying mechanism. 
      METHODS: ANGPTL4 expression in clinical patient tumor samples was determined by 
      immunohistochemistry (IHC) and high-throughput sequencing. ANGPTL4 knockdown (KD) 
      and the addition of exogeneous cANGPTL4 protein were used to investigate its 
      function. An in vivo xenograft tumor experiment was performed by intraperitoneal 
      injection of SKOV3 cells transfected with short hairpin RNAs (shRNAs) targeting 
      ANGPTL4 in nude mice. Western blotting and qRT-PCR were used to detect the levels 
      of ANGPTL4, CDH5, p-AKT, AKT, ETV5, MMP2 and MMP9 in SKOV3 and HO8910 cells 
      transfected with sh-ANGPTL4 or shRNAs targeting ETV5. RESULTS: Increased levels 
      of ANGPTL4 were associated with poor prognosis and metastasis in OC and induced 
      the angiogenesis and metastasis of OC cells both in vivo and in vitro. This 
      tumorigenic effect was dependent on CDH5, and the expression levels of ANGPTL4 
      and CDH5 in human OC werepositively correlated. In addition, CDH5 activated 
      p-AKT, and upregulated the expression of MMP2 and MMP9. We also found that the 
      expression of ETV5 was upregulated by ANGPTL4, which could bind the promoter 
      region of CDH5, leading to increased CDH5 expression. CONCLUSION: Our data 
      indicated that an increase in the ANGPTL4 level results in increased ETV5 
      expression in OC, leading to metastasis via activation of the CDH5/AKT/MMP9 
      signaling pathway.
CI  - (c) 2022. The Author(s).
FAU - Liu, Yinping
AU  - Liu Y
AD  - Qingpu Branch of Zhongshan Hospital, Fudan University, 1158 Gongyuandong Road, 
      Qingpu District, 201700, Shanghai, P. R. China.
AD  - Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, No. 85 Wujin Road, Hongkou, 200080, 
      Shanghai, P. R. China.
FAU - Yang, Rui
AU  - Yang R
AD  - Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, No. 85 Wujin Road, Hongkou, 200080, 
      Shanghai, P. R. China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, No. 85 Wujin Road, Hongkou, 200080, 
      Shanghai, P. R. China.
FAU - Zhu, Yaping
AU  - Zhu Y
AD  - Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, No. 85 Wujin Road, Hongkou, 200080, 
      Shanghai, P. R. China. zhuyp63@126.com.
FAU - Bao, Wei
AU  - Bao W
AD  - Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, No. 85 Wujin Road, Hongkou, 200080, 
      Shanghai, P. R. China. forever_chipper@hotmail.com.
AD  - Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, No. 85 Wujin Road, Hongkou, 201620, 
      Shanghai, P.R. China. forever_chipper@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20221214
PL  - England
TA  - J Ovarian Res
JT  - Journal of ovarian research
JID - 101474849
RN  - 0 (Angiopoietin-Like Protein 4)
RN  - 0 (ANGPTL4 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ETV5 protein, human)
RN  - 0 (Etv5 protein, mouse)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (MMP9 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factors)
RN  - 0 (cadherin 5)
SB  - IM
RIN - J Ovarian Res. 2023 Jan 26;16(1):23. PMID: 36698130
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - Angiopoietin-Like Protein 4/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - DNA-Binding Proteins
MH  - Matrix Metalloproteinase 2
MH  - Matrix Metalloproteinase 9/genetics
MH  - Mice, Nude
MH  - Oncogenes/genetics
MH  - *Ovarian Neoplasms/genetics/metabolism/pathology
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA, Small Interfering
MH  - Transcription Factors
PMC - PMC9749186
OTO - NOTNLM
OT  - ANGPTL4
OT  - Angiogenesis
OT  - CDH5
OT  - Ovarian cancer
COIS- The authors have no conflicts of interest to declare.
EDAT- 2022/12/15 06:00
MHDA- 2022/12/17 06:00
PMCR- 2022/12/14
CRDT- 2022/12/14 23:47
PHST- 2021/11/17 00:00 [received]
PHST- 2022/11/15 00:00 [accepted]
PHST- 2022/12/14 23:47 [entrez]
PHST- 2022/12/15 06:00 [pubmed]
PHST- 2022/12/17 06:00 [medline]
PHST- 2022/12/14 00:00 [pmc-release]
AID - 10.1186/s13048-022-01060-7 [pii]
AID - 1060 [pii]
AID - 10.1186/s13048-022-01060-7 [doi]
PST - epublish
SO  - J Ovarian Res. 2022 Dec 14;15(1):131. doi: 10.1186/s13048-022-01060-7.