Emerging evidence implicates the chromodomain helicase/ATPase DNA binding 
protein 1-like gene (CHD1L) as a specific oncogene in human hepatocellular 
carcinoma (HCC). To better understand the molecular mechanisms underlying HCC 
cases carrying CHD1L amplification (>50% HCCs), we identified a CHD1L target, 
translationally controlled tumor protein (TCTP), and investigated its role in 
HCC progression. Here, we report that CHD1L protein directly binds to the 
promoter region (nt -733 to -1,027) of TCTP and activates TCTP transcription. 
Overexpression of TCTP was detected in 40.7% of human HCC samples analyzed and 
positively correlated with CHD1L overexpression. Clinically, overexpression of 
TCTP was significantly associated with the advanced tumor stage (P = 0.037) and 
overall survival time of HCC patients (P = 0.034). In multivariate analyses, 
TCTP was determined to be an independent marker associated with poor prognostic 
outcomes. In vitro and in vivo functional studies in mice showed that TCTP has 
tumorigenic abilities, and overexpression of TCTP induced by CHD1L contributed 
to the mitotic defects of tumor cells. Further mechanistic studies demonstrated 
that TCTP promoted the ubiquitin-proteasome degradation of Cdc25C during mitotic 
progression, which caused the failure in the dephosphorylation of Cdk1 on Tyr15 
and decreased Cdk1 activity. As a consequence, the sudden drop of Cdk1 activity 
in mitosis induced a faster mitotic exit and chromosome missegregation, which 
led to chromosomal instability. The depletion experiment proved that the 
tumorigenicity of TCTP was linked to its role in mitotic defects.
CONCLUSION: Collectively, we reveal a novel molecular pathway 
(CHD1L/TCTP/Cdc25C/Cdk1), which causes the malignant transformation of 
hepatocytes with the phenotypes of accelerated mitotic progression and the 
production of aneuploidy.