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FRK suppresses the proliferation of human glioma cells by inhibiting cyclin D1 nuclear accumulation.
- Source :
-
Journal of neuro-oncology [J Neurooncol] 2014 Aug; Vol. 119 (1), pp. 49-58. Date of Electronic Publication: 2014 May 03. - Publication Year :
- 2014
-
Abstract
- The Fyn related kinase (FRK) is a noteworthy member of the Src non-receptor tyrosine kinase family for its distinctive tumor suppressive function. Recently, we have shown that FRK plays a protective role against the progression of glioma by suppressing cell migration and invasion. However, it is unclear whether the cell growth of glioma is also regulated by FRK and by which mechanism FRK alters its specific biological functions. In the current study, we found that FRK over-expression significantly suppressed the proliferation of glioma cells. In contrast, FRK knockdown by siRNA promoted glioma cell growth. In addition, FRK over-expression caused G1 phase arrest as well as apoptosis of glioma cells. Further investigation disclosed that FRK-induced G1 arrest was accompanied by down-regulation of hyperphosphorylated retinoblastoma protein (pRb), which led to the consequent suppression of E2F1. More importantly, we found that over-expression of FRK inhibited proper cyclin D1 accumulation in the nucleus of proliferating cells. Taken together, our results demonstrate a combined mechanism for the anti-proliferative effects of FRK by inhibiting cyclin D1 nucleus accumulation and pRb phosphorylation in glioma cells.
- Subjects :
- Brain Neoplasms pathology
Cell Line, Tumor
Down-Regulation
G1 Phase
Glioma pathology
Humans
Phosphorylation
Retinoblastoma Protein metabolism
Signal Transduction physiology
Brain Neoplasms metabolism
Cell Nucleus metabolism
Cell Proliferation physiology
Cyclin D1 metabolism
Glioma metabolism
Neoplasm Proteins metabolism
Protein-Tyrosine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7373
- Volume :
- 119
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24792491
- Full Text :
- https://doi.org/10.1007/s11060-014-1461-y