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2017 ; 13
(4
): 2599-2606
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Oct4 induces EMT through LEF1/?-catenin dependent WNT signaling pathway in
hepatocellular carcinoma
#MMPMID28454439
Sun L
; Liu T
; Zhang S
; Guo K
; Liu Y
Oncol Lett
2017[Apr]; 13
(4
): 2599-2606
PMID28454439
show ga
Octamer 4 (Oct4), a member of the Pit-Oct-Unc transcription factor family
required to maintain self-renewal and pluripotency of embryonic stem cells, has
been previously identified to be associated with tumorigenesis and malignant
transformation of numerous types of cancer including hepatocellular carcinoma
(HCC). The present data shows that Oct4 enhances cancer stem cell properties and
increases invasion ability in the Huh7 cell line. To increase understanding of
the role of Oct4 in HCC, the present study used a functional genomics approach
and analyzed the resulting transcriptional profiles to identify Oct4-dependent
genes in Huh7. Affymetrix GeneChip Human genome U133 Plus 2.0 Arrays were used to
determine differential gene expression profiles and then validated by
quantitative polymerase chain reaction. The present study found that altered
expression of 673 genes (fold-change ?2) affected multiple signaling pathways
linked with self-renew and metastasis. Among these differentially expressed
genes, the present study noticed that the key component of the WNT signaling
pathway lymphoid enhancer binding factor 1 (LEF1) and Twist Family BHLH
transcription factor 1 were upregulated by Oct4, whilst cadherin 2 was
downregulated. Additional studies found that the nuclear ?-catenin aggregation
was increased in Oct4 overexpressed HCC cell lines. These results suggest that
Oct4 regulates LEF1 to active LEF1/?-catenin dependent WNT signaling pathway and
promote epithelial-mesenchymal transition. The present findings provide novel
mechanistic insight into an important role of Oct4 in HCC.