The downregulation of choline kinase alpha inhibits clear cell renal cell carcinoma proliferation and metastasis via the MAPK and PI3K/AKT pathways

被引：0

作者：

Zhang, Feng-Shi ^{[1
]}

Hong, Yang ^{[1
]}

Zhu, Zhen-Jie ^{[1
]}

An, Li-Zhe ^{[1
]}

Huang, Xiao-Bo ^{[1
]}

Xu, Qing-Quan ^{[1
]}

机构：

[1] Peking Univ Peoples Hosp, Urol & Lithotripsy Ctr, 133 FUCHENGMENNEI St, Beijing 100034, Peoples R China

来源：

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE | 2019年 / 12卷 / 06期

关键词：

CHKA; renal cell carcinoma; prognosis; proliferation; GROWTH-FACTOR RECEPTOR; PHOSPHOLIPID-METABOLISM; CYCLE REGULATION; DRUG-RESISTANCE; CANCER; OVEREXPRESSION; EXPRESSION; TARGET; PHOSPHOCHOLINE; AGGRESSIVENESS;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The abnormal expression of choline kinase alpha (CHKA) is associated with the development and progression of a variety of human malignancies. This study found that in patients with clear cell renal cell carcinoma (ccRCC), the overall survival of the CHKA high expression group was significantly shorter than the CHKA low expression group. The expression of CHKA in the ccRCC metastatic cell line was significantly higher than the expressions in the non-metastatic cell lines. The results of CCK-8, colony formation, Transwell and Matrigel assays showed that the knockdown of CHKA had a significant effect on the cell proliferation, migration and invasion of ccRCC. In addition, flow cytometry results showed that CHKA knockdown induced G0-G1 arrest and cell apoptosis. Mechanistic studies suggest that CHKA can promote the progression of ccRCC by altering the expression of Phospho-ERK, Phospho-AKT (Ser473), Cyclin D1, and caspase-3. Overall, our study suggests that CHKA contributes to the progression and metastasis of ccRCC and may serve as a new prognostic biomarker and potential therapeutic target.

引用

页码：6768 / 6778

页数：11

共 58 条

[21] Choline metabolism in malignant transformation [J].

Glunde, Kristine ;

Bhujwalla, Zaver M. ;

Ronen, Sabrina M. .

NATURE REVIEWS CANCER, 2011, 11 (12) :835-848

[22] Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer [J].

Granata, A. ;

Nicoletti, R. ;

Tinaglia, V. ;

De Cecco, L. ;

Pisanu, M. E. ;

Ricci, A. ;

Podo, F. ;

Canevari, S. ;

Iorio, E. ;

Bagnoli, M. ;

Mezzanzanica, D. .

BRITISH JOURNAL OF CANCER, 2014, 110 (02) :330-340

[23] Balance of human choline kinase isoforms is critical for cell cycle regulation Implications for the development of choline kinase-targeted cancer therapy [J].

Gruber, Jens ;

Too, Wei Cun See ;

Wong, Mun Teng ;

Lavie, Arnon ;

McSorley, Theresa ;

Konrad, Manfred .

FEBS JOURNAL, 2012, 279 (11) :1915-1928

[24]

Hernández-Alcoceba R, 1999, CANCER RES, V59, P3112

[25] A critical role for choline kinase-α in the aggressiveness of bladder carcinomas [J].

Hernando, E. ;

Sarmentero-Estrada, J. ;

Koppie, T. ;

Belda-Iniesta, C. ;

de Molina, V. Ramirez ;

Cejas, P. ;

Ozu, C. ;

Le, C. ;

Sanchez, J. J. ;

Gonzalez-Baron, M. ;

Koutcher, J. ;

Cordon-Cardo, C. ;

Bochner, B. H. ;

Lacal, J. C. ;

de Molina, A. Ramirez .

ONCOGENE, 2009, 28 (26) :2425-2435

[26] Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma [J].

Hu, Liang ;

Wang, Ruo-Yu ;

Cai, Jian ;

Feng, Dan ;

Yang, Guang-Zhen ;

Xu, Qing-Guo ;

Zhai, Yan-Xia ;

Zhang, Yu ;

Zhou, Wei-Ping ;

Cai, Qing-Ping .

ONCOTARGET, 2016, 7 (41) :66660-66678

[27]

Jemal A, 2011, CA-CANCER J CLIN, V61, P134, DOI [10.3322/caac.20115, 10.3322/caac.21492, 10.3322/caac.20107]

[28] METABOLISM OF LIPIDES [J].

KENNEDY, EP .

ANNUAL REVIEW OF BIOCHEMISTRY, 1957, 26 :119-148

[29] Choline Kinase Alpha and Hexokinase-2 Protein Expression in Hepatocellular Carcinoma: Association with Survival [J].

Kwee, Sandi A. ;

Hernandez, Brenda ;

Chan, Owen ;

Wong, Linda .

PLOS ONE, 2012, 7 (10)

[30] Preclinical Characterization of RSM-932A, a Novel Anticancer Drug Targeting the Human Choline Kinase Alpha, an Enzyme Involved in Increased Lipid Metabolism of Cancer Cells [J].

Lacal, Juan Carlos ;

Campos, Joaquin M. .

MOLECULAR CANCER THERAPEUTICS, 2015, 14 (01) :31-39

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