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2017 ; 8
(36
): 60173-60187
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
5-Azacytidine promotes invadopodia formation and tumor metastasis through the
upregulation of PI3K in ovarian cancer cells
#MMPMID28947962
Cao D
; Li D
; Huang Y
; Ma Y
; Zhang B
; Zhao C
; Deng S
; Luo M
; Yin T
; Wei YQ
; Wang W
Oncotarget
2017[Sep]; 8
(36
): 60173-60187
PMID28947962
show ga
The high incidence of metastasis accounts for most of the lethality of ovarian
cancer. Invadopodia are small, specialized types of machinery that degrade the
extracellular matrix and are thus involved in the invasion and metastasis of
cancer cells. The formation of invadopodia is regulated by both genetic and
epigenetic factors. However, the ways by which methylation/demethylation
regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In
this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine)
increased the formation of invadopodia and enhanced degradation of the
extracellular matrix in ovarian cancer cells. In mouse xenograft models,
treatment with 5-AZ increased the number of metastatic nodules, which suggests an
elevated potential for metastasis by demethylation. Further investigation
indicated that the inhibition of methylation elevated the transcription of PIK3CA
and upregulated genes involved in the PI3K-AKT signaling pathway. In addition,
this induction likely occurs though the epigenetic regulation of PIK3CA because
analyses of the DNA methylation level of the PIK3CA promoter region found that
5-AZ treatment decreased the methylation of CpG islands in SKOV3 and A2780 cells.
Our study demonstrated that epigenetic factors regulate the metastatic potential
of ovarian cancer cells and provide rationale for therapies that inhibit PI3K-
invadopodia-mediated metastasis.