title: FRK suppresses the proliferation of human glioma cells by inhibiting cyclin D1 nuclear accumulation.
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.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hua
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Xu
authors.initials: X
authors.lastname: Song
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Fang
authors.forename: Chunting
authors.initials: C
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhan
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Qingming
authors.initials: Q
authors.lastname: Meng
authors.forename: Xiuping
authors.initials: X
authors.lastname: Zhou
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism*; D015536:Down-Regulation; D016193:G1 Phase; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human