RACK1 promotes lung cancer cell growth via an MCM7/RACK1/Akt signaling complex

被引:34
|
作者
Fei, Liangru [1 ]
Ma, Yinan [1 ]
Zhang, Meiyu [1 ]
Liu, Xiaofang [2 ]
Luo, Yuan [1 ]
Wang, Congcong [2 ]
Zhang, Haiyan [3 ]
Zhang, Wenzhu [1 ]
Han, Yuchen [1 ,2 ]
机构
[1] China Med Univ, Sch Basic Med Sci, Dept Pathol, Shenyang 110000, Peoples R China
[2] China Med Univ, Dept Pathol, Affiliated Hosp 1, Shenyang 110000, Peoples R China
[3] First Peoples Hosp Jining, Dept Pathol, Jining 272000, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
RACK1; MCM7; proliferation; NSCLC; Akt; MINICHROMOSOME MAINTENANCE PROTEIN-7; ACTIVATED C KINASE; DNA HELICASE ACTIVITY; TYROSINE PHOSPHORYLATION; MCM PROTEINS; BETA-SUBUNIT; PROGNOSTIC-SIGNIFICANCE; PROSTATE-CANCER; SRC ACTIVITY; REPLICATION;
D O I
10.18632/oncotarget.17120
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MCM7, a member of the miniature chromosome maintenance (MCM) protein family, is crucial for the initiation of DNA replication and proliferation in eukaryotic cells. In this report, we demonstrate that RACK1 regulates cell growth and cell cycle progression in human non-small-cell lung cancer by mediating MCM7 phosphorylation through an MCM7/RACK1/Akt signaling complex. RACK1 functions as a central scaffold that brings Akt into physical proximity with MCM7. Overexpression of RACK1 increases interactions between Akt and MCM7 and promotes Akt-dependent MCM7 phosphorylation, which in turn increases MCM7 binding to chromatin and MCM complex formation. Together, these changes promote DNA replication and cell proliferation. Our findings reveal a novel signaling pathway that regulates growth in non-small cell lung cancer.
引用
收藏
页码:40501 / 40513
页数:13
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