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PMID:17909029

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Citation

Kim, J, Jahng, WJ, Di Vizio, D, Lee, JS, Jhaveri, R, Rubin, MA, Shisheva, A and Freeman, MR (2007) The phosphoinositide kinase PIKfyve mediates epidermal growth factor receptor trafficking to the nucleus. Cancer Res. 67:9229-37

Abstract

ErbB receptor tyrosine kinases can transit to nuclei in tumor cells, where they have been shown to regulate gene expression as components of transcriptional complexes. Quantitative analysis of a human bladder cancer tissue microarray identified nuclear epidermal growth factor receptor (EGFR) in tumor cells and also showed an increased frequency of this histologic feature in cancer relative to normal tissues. This observation suggests a potential role for nuclear EGFR in bladder cancer. We confirmed that EGFR could be induced to transit to nuclei in cultured human bladder cancer cells in response to the urothelial cell growth factor and EGFR ligand heparin-binding EGF-like growth factor (HB-EGF). Mass spectrometric analysis of EGFR immune complexes from a transitional carcinoma cell line (TCCSUP) identified the phosphoinositide kinase, PIKfyve, as a potential component of the EGFR trafficking mechanism. RNA silencing indicated that PIKfyve is a mediator of HB-EGF-stimulated EGFR nuclear trafficking, EGFR binding to the cyclin D1 promoter, and cell cycle progression. These results identify a novel mediator of the EGFR transcription function and further suggest that nuclear EGFR and the lipid kinase PIKfyve may play a role in bladder oncogenesis.

Links

PubMed Online version:10.1158/0008-5472.CAN-07-1333

Keywords

Cell Line, Tumor; Cell Nucleus/enzymology; Cyclin D1/genetics; Humans; Immunohistochemistry; Mass Spectrometry; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism; Promoter Regions, Genetic; Protein Binding; RNA, Small Interfering/genetics; Receptor, Epidermal Growth Factor/genetics; Receptor, Epidermal Growth Factor/metabolism; Signal Transduction; Transfection; Urinary Bladder Neoplasms/enzymology; Urinary Bladder Neoplasms/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:EGFR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Y2I7

F

Seeded From UniProt

complete

HUMAN:FYV1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P00533

F

Seeded From UniProt

complete

HUMAN:FYV1

involved_in

GO:0034504: protein localization to nucleus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:EGFR_original

GO:0005515: protein binding

IPI: Inferred from Physical Interaction: UniProtKB:Q9Y2I7

F


See also

References

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