CDKL3 promotes osteosarcoma progression by activating Akt/PKB

被引：15

作者：

He, Aina ^{[1
,2
]}

Ma, Lanjing ^{[3
]}

Huang, Yujing ^{[1
]}

Zhang, Haijiao ^{[3
]}

Duan, Wei ^{[4
,5
]}

Li, Zexu ^{[3
]}

Fei, Teng ^{[3
]}

Yuan, Junqing ^{[6
]}

Wu, Hao ^{[7
]}

Liu, Liguo ^{[8
]}

Bai, Yueqing ^{[6
]}

Dai, Wentao ^{[9
,10
]}

Wang, Yonggang ^{[1
]}

Li, Hongtao ^{[1
]}

Sun, Yong ^{[1
]}

Wang, Yaling ^{[1
]}

Wang, Chunyan ^{[1
]}

Yuan, Ting ^{[11
]}

Yang, Qingcheng ^{[11
]}

Tian, Songhai ^{[2
]}

Dong, Min ^{[2
]}

Sheng, Ren ^{[3
]}

Xiang, Dongxi ^{[12
,13
,14
]}

机构：

[1] Shanghai Jiaotong Univ Affiliated Peoples Hosp 6, Dept Oncol, Shanghai, Peoples R China

[2] Harvard Med Sch, Boston Childrens Hosp, Dept Urol, Boston, MA 02115 USA

[3] Northeastern Univ, Coll Life & Hlth Sci, Shenyang, Peoples R China

[4] Deakin Univ, Sch Med, Waurn Ponds, Vic, Australia

[5] Deakin Univ, Ctr Mol & Med Res, Waurn Ponds, Vic, Australia

[6] Shanghai Jiaotong Univ Affiliated Peoples Hosp 6, Dept Pathol, Shanghai, Peoples R China

[7] Boston Childrens Hosp, Dept Vasc Biol, Boston, MA USA

[8] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gen Surg, Shanghai, Peoples R China

[9] Shanghai Ind Technol Inst, Shanghai Ctr Bioinformat Technol, Shanghai, Peoples R China

[10] Shanghai Ind Technol Inst, Shanghai Engn Res Ctr Pharmaceut Translat, Shanghai, Peoples R China

[11] Shanghai Jiaotong Univ Affiliated Peoples Hosp 6, Dept Orthoped, Shanghai, Peoples R China

[12] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA

[13] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[14] Shanghai Jiao Tong Univ, Sch Med, Shanghai Res Ctr Biliary Tract Dis, Shanghai, Peoples R China

来源：

LIFE SCIENCE ALLIANCE | 2020年 / 3卷 / 05期

基金：

中国国家自然科学基金; 上海市自然科学基金; 国家重点研发计划;

关键词：

CANCER-CELLS; IN-VITRO; PROTEIN; SENESCENCE; PATHWAY; AKT; KINASE; GROWTH; GENE; PHOSPHORYLATION;

D O I：

10.26508/lsa.202000648

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Osteosarcoma (OS) is a primary malignant bone neoplasm with high frequencies of tumor metastasis and recurrence. Although the Akt/PKB signaling pathway is known to play key roles in tumorigenesis, the roles of cyclin-dependent kinase-like 3 (CDKL3) in OS progression remain largely elusive. We have demonstrated the high expression levels of CDKL3 in OS human specimens and comprehensively investigated the role of CDKL3 in promoting OS progression both in vitro and in vivo. We found that CDKL3 regulates Akt activation and its downstream effects, including cell growth and autophagy. The up-regulation of CDKL3 in OS specimens appeared to be associated with Akt activation and shorter overall patient survival (P=0.003). Our findings identify CDKL3 as a critical regulator that stimulates OS progression by enhancing Akt activation. CDKL3 represents both a biomarker for OS prognosis, and a potential therapeutic target in precision medicine by targeting CDKL3 to treat Akt hyper-activated OS.

引用

页数：16

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