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2015 ; 14
(ä): 66
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PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing
NF-?B/MMP-9 signaling pathway
#MMPMID25888829
Shi M
; Cao M
; Song J
; Liu Q
; Li H
; Meng F
; Pan Z
; Bai J
; Zheng J
Mol Cancer
2015[Mar]; 14
(ä): 66
PMID25888829
show ga
BACKGROUND: PinX1 (PIN2/TRF1-interacting telomerase inhibitor 1) was suggested to
be correlated with tumor progression. This study was designed to evaluate the
role of PinX1 in human breast cancer. METHODS: To evaluate the function of PinX1
in breast cancer, we used a tissue microarray (TMA) of 405 human breast cancer
patients and immunohistochemistry to analyze the correlation between PinX1
expression and clinicopathologic variables and patient survival. We also detected
the abilities of cell migration and invasion in breast cancer by performing cell
migration and invasion assay, gelatin zymography and western blot analysis.
Lastly, we set up the nude mice model by Tail vein assay to exam the functional
role of PinX1 in breast cancer metastasis. RESULTS: We found that low PinX1
expression was associated with lymph node metastasis (P?=?0.002) and histology
grade (P?=?0.001) in patients, as well as with poorer overall and
disease-specific survival (P?=?0.010 and P?=?0.003, respectively). Moreover, we
identified that PinX1 inhibited the migration and invasion of breast cancer by
suppressing MMP-9 expression and activity via NF-?B-dependent transcription in
vitro. Finally, our mice model confirmed that PinX1 suppressed breast cancer
metastasis in vivo. CONCLUSIONS: Our data revealed that low PinX1 expression was
an independent negative prognostic factor for breast cancer patients. These
findings suggested that PinX1 might be function as a tumor metastasis suppressor
in the development and progression of breast cancer by regulating the NF-?B/MMP-9
signaling pathway, and might be a prognostic marker as well as a therapeutic
target for breast cancer.