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Polycystin-1 induces activation of the PI3K/AKT/mTOR pathway and promotes angiogenesis in renal cell carcinoma
- Source :
- Cancer Letters. 489:135-143
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- 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.
- Subjects :
- Adult
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
endocrine system
Cancer Research
TRPP Cation Channels
Angiogenesis
urologic and male genital diseases
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Movement
Polycystic kidney disease
medicine
Humans
Carcinoma, Renal Cell
Protein kinase B
PI3K/AKT/mTOR pathway
Aged
Cell Proliferation
Retrospective Studies
Neovascularization, Pathologic
Chemistry
Cell growth
TOR Serine-Threonine Kinases
Cell migration
Middle Aged
medicine.disease
Kidney Neoplasms
female genital diseases and pregnancy complications
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
Phosphorylation
Female
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 489
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....8c24f8b43a8e342363a44c92c7bec8fc