PMID- 32104684
OWN - NLM
STAT- MEDLINE
DCOM- 20201119
LR  - 20201119
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2020
DP  - 2020
TI  - Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits 
      Clear Cell Renal Cell Carcinoma.
PG  - 2527643
LID - 10.1155/2020/2527643 [doi]
LID - 2527643
AB  - Targeted therapy for kidney cancer has achieved significant clinical results. 
      However, because most patients who use targeted therapy will develop drug 
      resistance, we still need to constantly explore new therapeutic targets. Although 
      porcupine (PORCN) as a palmitoyltransferase plays a crucial role in the 
      activation and secretion of Wnt proteins and affects the activity of the Wnt 
      signaling pathway, little is known about the role of PORCN in clear cell renal 
      cell carcinoma (ccRCC). We found that PORCN is highly expressed in renal cancer 
      cell lines and patients with renal cell carcinoma with high expression of PORCN 
      have a poor prognosis. Pathway analysis of PORCN and its related proteins showed 
      that PORCN played a role through the Wnt signaling pathway, and there was a 
      strong coexpression relationship between PORCN and Wnt proteins. Therefore, PORCN 
      may be a potential and effective target for ccRCC. In the present study, we found 
      that LGK974 could inhibit proliferation and colony formation and induce apoptosis 
      in ccRCC cells. We also found that LGK974 could inhibit the migration and 
      invasion of renal cell carcinoma and reduce the expression of mesenchymal 
      markers. After treatment with LGK974, the expression level of beta-catenin, a key 
      protein in the classical Wnt pathway, was significantly decreased, and the 
      expression levels of the target genes cyclin D1, c-Myc, MMP9, and MMP2 in the Wnt 
      signaling pathway were also significantly decreased, which represented a 
      significant decrease in the activity of the Wnt signaling pathway. At the same 
      time, the cycle of renal cancer cells was significantly blocked. In conclusion, 
      our results indicate that LGK974 could significantly inhibit the progression of 
      renal cancer cells in a safe concentration range, so PORCN may be a safe and 
      effective target for patients with renal cancer.
CI  - Copyright (c) 2020 Jianyi Li et al.
FAU - Li, Jianyi
AU  - Li J
AD  - Department of Urology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
FAU - Wu, Guangzhen
AU  - Wu G
AUID- ORCID: 0000-0002-2300-8465
AD  - Department of Urology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
AD  - Department of Urology, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Xu, Yingkun
AU  - Xu Y
AD  - Department of Urology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
FAU - Li, Jiatong
AU  - Li J
AD  - Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong 
      First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
FAU - Ruan, Ningke
AU  - Ruan N
AD  - The Nursing College of Zhengzhou University, Zhengzhou, China.
FAU - Chen, Yougen
AU  - Chen Y
AD  - Department of Urology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Department of Urology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
FAU - Xia, Qinghua
AU  - Xia Q
AUID- ORCID: 0000-0002-8261-6014
AD  - Department of Urology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20200213
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Pyrazines)
RN  - 0 (Pyridines)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (PORCN protein, human)
RN  - U27F40013Q (LGK974)
SB  - IM
MH  - Acyltransferases/*antagonists & inhibitors/metabolism
MH  - Carcinoma, Renal Cell/drug therapy/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Down-Regulation/*drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Kidney Neoplasms/drug therapy/*metabolism/pathology
MH  - Membrane Proteins/*antagonists & inhibitors/metabolism
MH  - *Neoplasm Proteins/antagonists & inhibitors/metabolism
MH  - Pyrazines/*pharmacology
MH  - Pyridines/*pharmacology
MH  - Wnt Signaling Pathway/*drug effects
PMC - PMC7040395
COIS- The authors declare that there are no conflicts of interest regarding the 
      publication of this paper.
EDAT- 2020/02/28 06:00
MHDA- 2020/11/20 06:00
PMCR- 2020/02/13
CRDT- 2020/02/28 06:00
PHST- 2019/10/24 00:00 [received]
PHST- 2019/12/30 00:00 [accepted]
PHST- 2020/02/28 06:00 [entrez]
PHST- 2020/02/28 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2020/02/13 00:00 [pmc-release]
AID - 10.1155/2020/2527643 [doi]
PST - epublish
SO  - Biomed Res Int. 2020 Feb 13;2020:2527643. doi: 10.1155/2020/2527643. eCollection 
      2020.