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2017 ; 36
(1
): 65
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AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways
in triple-negative breast cancer
#MMPMID28494797
Chen B
; Wang J
; Dai D
; Zhou Q
; Guo X
; Tian Z
; Huang X
; Yang L
; Tang H
; Xie X
J Exp Clin Cancer Res
2017[May]; 36
(1
): 65
PMID28494797
show ga
BACKGROUND: AHNAK, also known as desmoyokin, is a giant protein with the
molecular size of approximately 700 kDa and exerts diverse functions in different
types of cancer. RESULTS: In the present study, we demonstrated that AHNAK mRNA
levels were down-regulated in 7 out of 8 human breast cancer cell lines,
especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in
patients with TNBC, the expression of AHNAK gene was inversely correlated with
the tumor status (P?=?0.015), lymph node status (P?0.001), lymph node (LN)
infiltration (P?0.001) and TNM stage (P?0.001). Moreover, down-regulated
AHNAK expression was considered an independent prognostic factor associated with
the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell
lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and
colony formation, and inhibited the in vivo TNBC xenograft growth and lung
metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the
AKT/MAPK signaling pathway and Wnt/?-catenin pathway. Consistent results were
observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells. CONCLUSIONS:
Taken together, our results suggest that AHNAK acts as a tumor suppressor that
negatively regulates TNBC cell proliferation, TNBC xenograft growth and
metastasis via different signaling pathways.
|*Signal Transduction
[MESH]
|Adult
[MESH]
|Aged
[MESH]
|Animals
[MESH]
|Apoptosis
[MESH]
|Cell Line, Tumor
[MESH]
|Cell Movement
[MESH]
|Cell Proliferation
[MESH]
|Computational Biology/methods
[MESH]
|Disease Models, Animal
[MESH]
|Female
[MESH]
|Gene Expression
[MESH]
|Gene Expression Profiling
[MESH]
|Heterografts
[MESH]
|Humans
[MESH]
|MAP Kinase Signaling System
[MESH]
|Membrane Proteins/*genetics/*metabolism
[MESH]
|Mice
[MESH]
|Middle Aged
[MESH]
|Neoplasm Grading
[MESH]
|Neoplasm Metastasis
[MESH]
|Neoplasm Proteins/*genetics/*metabolism
[MESH]
|Neoplasm Staging
[MESH]
|Proto-Oncogene Proteins c-akt/metabolism
[MESH]
|Triple Negative Breast Neoplasms/*genetics/*metabolism/mortality/pathology
[MESH]