Abstract
BackgroundPinX1 (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.MethodsTo 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.ResultsWe 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-κB-dependent transcription in vitro. Finally, our mice model confirmed that PinX1 suppressed breast cancer metastasis in vivo.ConclusionsOur 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-κB/MMP-9 signaling pathway, and might be a prognostic marker as well as a therapeutic target for breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0332-2) contains supplementary material, which is available to authorized users.
Highlights
Breast cancer is the most common malignancy of the female, and its survival rate falls from 90% for localized to 20% for metastatic disease [1]
We demonstrated that PIN2/telomeric repeat binding factor 1 (TRF1)-interacting telomerase inhibitor 1 (PinX1) suppressed breast cancer migration and invasion by inhibiting the expression and activity of matrix metalloproteinase (MMP)-9 via NF-κB-dependent transcription in vitro and in vivo
Correlation of PinX1 staining with clinicopathologic parameters in breast cancer patients To investigate PinX1 expression in breast cancer, immunohistochemistry was carried out in tissue microarray (TMA) slides (Figure 1A)
Summary
Breast cancer is the most common malignancy of the female, and its survival rate falls from 90% for localized to 20% for metastatic disease [1]. Human telomerase is a ribonucleoprotein, mainly consisting of catalytic subunit hTERT and RNA template hTR, which involves in malignant tumor formation [5,6,7]. Human telomerase reverse transcriptase (hTERT), containing two conserved N-terminal and four C-terminal domains essential for telomerase catalytic activity, is referred as the rate-limiting step of telomerase activation [8]. Telomerase expression is suppressed in most normal cells, whereas reactivated in more than 85% of human cancer cells [9,10]. 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
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