RGD Reference Report - PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3ß/CTNNB1 signaling pathway. - Rat Genome Database

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PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3ß/CTNNB1 signaling pathway.

Authors: Lin, Youcheng  Yang, Zhao  Xu, Abai  Dong, Pei  Huang, Yi  Liu, Huan  Li, Feida  Wang, Haifeng  Xu, Qian  Wang, Yongqiang  Sun, Da  Zou, Yong  Zou, Xiaowen  Wang, Yu  Zhang, Duo  Liu, Hongjie  Wu, Xun  Zhang, Meng  Fu, Yu  Cai, Zhiming  Liu, Chunxiao  Wu, Song 
Citation: Lin Y, etal., Sci Rep. 2015 Mar 11;5:8997. doi: 10.1038/srep08997.
RGD ID: 13504823
Pubmed: PMID:25757764   (View Abstract at PubMed)
PMCID: PMC4355729   (View Article at PubMed Central)
DOI: DOI:10.1038/srep08997   (Journal Full-text)

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been identified as an important pathway in renal cell carcinoma (RCC). We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry and real-time polymerase chain reaction. The expression of PIK3R1 significantly decreased in pRCC and was further reduced in mRCC compared with normal tissue. Besides, its expression levels were negatively correlated with T-category of tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial-mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown of AKT by shRNA reduced p-GSK3ß and CTNNB1 expression in the cells, while the depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1 down-regulation in RCC promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells through the AKT/GSK3ß/CTNNB1 pathway, and may contribute to progression and metastasis of RCC.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PIK3R1Humanrenal cell carcinoma disease_progressionIEP  RGD 
Pik3r1Ratrenal cell carcinoma disease_progressionISOPIK3R1 (Homo sapiens) RGD 
Pik3r1Mouserenal cell carcinoma disease_progressionISOPIK3R1 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Mus musculus)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Homo sapiens)
PIK3R1  (phosphoinositide-3-kinase regulatory subunit 1)


Additional Information