Protumorigenic role of Timeless in hepatocellular carcinoma

被引：42

作者：

Elgohary, Nahla ^{[1
,2
]}

Pellegrino, Rossella ^{[1
]}

Neumann, Olaf ^{[1
]}

Elzawahry, Heba M. ^{[2
]}

Saber, Magdy M. ^{[2
]}

Zeeneldin, Ahmed A. ^{[2
]}

Geffers, Robert ^{[3
]}

Ehemann, Volker ^{[1
]}

Schemmer, Peter ^{[4
]}

Schirmacher, Peter ^{[1
]}

Longerich, Thomas ^{[1
]}

机构：

[1] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany

[2] Cairo Univ, Dept Med Oncol NCI, Cairo 11796, Egypt

[3] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany

[4] Univ Heidelberg Hosp, Dept Gen Surg, D-69120 Heidelberg, Germany

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2015年 / 46卷 / 02期

关键词：

circadian clock genes; oncogene; hepatocellular carcinoma; ELONGATION-FACTOR EEF1A2; CIRCADIAN GENE TIMELESS; ACTIN CYTOSKELETON; MAMMALIAN TIMELESS; FACTOR; 1A; IN-VIVO; EXPRESSION; CANCER; REPLICATION; PROTEIN;

D O I：

10.3892/ijo.2014.2751

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The mammalian timeless (TIM) protein interacts with proteins of the endogenous clock and essentially contributes to the circadian rhythm. In addition, TIM is involved in maintenance of chromosome integrity, growth control and development. Thus, we hypothesized that TIM may exert a potential protumorigenic function in human hepatocarcinogenesis. TIM was overexpressed in a subset of human HCCs both at the mRNA and the protein level. siRNA-mediated knockdown of TIM reduced cell viability due to the induction of apoptosis and G2 arrest. The latter was mediated via CHEK2 phosphorylation. In addition, siRNA-treated cells showed a significantly reduced migratory capacity and reduced expression levels of various proteins. Mechanistically, TIM directly interacts with the eukaryotic elongation factor 1A2 (EEF1A2), which binds to actin filaments to promote tumor cell migration. siRNA-mediated knockdown of TIM reduced EEF1A2 protein levels thereby affecting ribosomal protein biosynthesis. Thus, overexPression of TIM exerts oncogenic function in human HCCs, which is mediated via CHEK2 and EEF1A2.

引用

页码：597 / 606

页数：10

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