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2017 ; 8
(33
): 54265-54276
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ING5 knockdown enhances migration and invasion of lung cancer cells by inducing
EMT via EGFR/PI3K/Akt and IL-6/STAT3 signaling pathways
#MMPMID28903339
Liu XL
; Zhang XT
; Meng J
; Zhang HF
; Zhao Y
; Li C
; Sun Y
; Mei QB
; Zhang F
; Zhang T
Oncotarget
2017[Aug]; 8
(33
): 54265-54276
PMID28903339
show ga
ING5 belongs to the Inhibitor of Growth (ING) candidate tumor suppressor family,
whose functions have been involved in the regulation of chromatin remodeling,
cell cycle progression, proliferation and apoptosis. Our previous study has shown
that ING5 overexpression inhibits lung cancer aggressiveness via suppressing
epithelial to mesenchymal transition (EMT). However, the mechanisms remain
largely unknown. In the current study, by Phospho-Kinase array and western blot,
we have defined significantly upregulated EGFR/PI3K/Akt and IL-6/STAT3 oncogenic
signaling pathways in ING5 knockdown A549 cells, which could be downregulated by
ING5 overexpression. PI3K inhibitor ZSTK474 or STAT3 inhibitor Niclosamide not
only abolished ING5 knockdown-promoted proliferation, colony formation, migration
and invasion of lung cancer A549 cells, but also impaired ING5
knockdown-stimulated metastasis of cancer cells in mouse xenograft models with
tail vein injection of A549 cells. Furthermore, treatment with ZSTK474 or
Niclosamide decreased protein level of EGFR, p-Akt, IL-6 and p-STAT3, and
reversed ING5 knockdown-promoted EMT, as indicated by downregulated expression of
EMT marker E-cadherin, an epithelial marker, increased expression of N-cadherin,
a mesenchymal marker, and EMT-related transcription factors including Snail,
Slug, Smad3 and Twist. Taken together, these results demonstrate that loss of
ING5 enhances aggressiveness of lung cancer cells by promoting EMT via activation
of EGFR/PI3K/Akt and IL-6/STAT3 signaling pathways.