Polycystin-1 induces activation of the PI3K/AKT/mTOR pathway and promotes angiogenesis in renal cell carcinoma.
Adult
Aged
Carcinoma, Renal Cell
/ pathology
Cell Movement
/ physiology
Cell Proliferation
/ physiology
Female
Humans
Kidney Neoplasms
/ pathology
Male
Middle Aged
Neovascularization, Pathologic
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Retrospective Studies
Signal Transduction
/ physiology
TOR Serine-Threonine Kinases
/ metabolism
TRPP Cation Channels
/ metabolism
Vascular Endothelial Growth Factor A
/ metabolism
PI3K
Polycystic kidney disease
Polycystin
Renal cell carcinoma
VEGF
mTOR
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
07
05
2020
revised:
03
06
2020
accepted:
13
06
2020
pubmed:
21
6
2020
medline:
16
1
2021
entrez:
21
6
2020
Statut:
ppublish
Résumé
In the present study we investigated the expression and the functional role of mechanosensitive polycystins in renal cell carcinoma (RCC). In 115 RCC patients we evaluated the protein expression of polycystin-1 (PC1), polycystin-2 (PC2), VEGF and protein components of the PI3K/Akt/mTOR pathway, which have been implicated both in RCC and polycystic kidney disease. PC1 and PC2 demonstrated reduced expression throughout the RCC tissue compared to the adjacent normal tissue. PC1 and PC2 revealed high expression when they were associated with higher grade and decreased 5-year survival respectively. PC1 and PC2 were positively correlated with p110γ subunit of PI3K and high PC1 expressing cells tended to display activation/phosphorylation of Akt. There was also a positive association between PC1 and VEGF expression, whereas PC1 augmented the tumor's microvascular network in stage IV carcinomas. In human RCC cells, functional inhibition of PC1 resulted in upregulation of the PI3K/Akt/mTOR pathway, enhanced cell proliferation and led to inhibition of cell migration. Conclusively, aberrant PC1 regulation is associated with increased angiogenesis and features of advanced disease in RCC tissues.
Identifiants
pubmed: 32561414
pii: S0304-3835(20)30347-5
doi: 10.1016/j.canlet.2020.06.016
pii:
doi:
Substances chimiques
TRPP Cation Channels
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
polycystic kidney disease 1 protein
0
polycystic kidney disease 2 protein
0
MTOR protein, human
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
135-143Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.