Prostate tumour overexpressed-1 promotes tumourigenicity in human breast cancer via activation of Wnt/β-catenin signalling

Abstract

Breast cancer is the most common malignancy in females. The presence of cancer stem cells (CSCs) is the main cause of local and distant tumour recurrence and is associated with poor outcome in breast cancer. However, the molecular mechanisms underlying the maintenance of CSCs remain largely unknown. This study demonstrates that prostate tumour overexpressed-1 (PTOV1) enhances the CSC population and augments the tumourigenicity of breast cancer cells both in vitro and in vivo. Moreover, PTOV1 suppresses transcription of Dickkopf-1 (DKK1) by recruiting histone deacetylases and subsequently reducing DKK1 promoter histone acetylation, followed by activation of Wnt/β-catenin signalling. Restoration of DKK1 expression in PTOV1-overexpressing cells counteracts the effects of PTOV1 on Wnt/β-catenin activation and the CSC population. Collectively, these results suggest that PTOV1 positively regulates the Wnt/β-catenin signalling pathway and enhances tumourigenicity in breast cancer; this novel mechanism may represent a therapeutic target for breast cancer. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

miR-150 inhibits proliferation and tumorigenicity via retarding G1/S phase transition in nasopharyngeal carcinoma

“…The relative expression levels of miR-150, CCND1, CCND2, CKD2 and CCNE2 after normalization were used to perform the correlation analysis among miR-150 and CCND1, CCND2, CKD2 and CCNE2 expression. This analysis method of clinical correlation was widely used in multiple lines of studies (34,35). The analysis of clinical correlation revealed that a significant inverse correlation was found between miR-150 and CCND1 (r=−0.841; P<0.05), CCND2 (r=−0.668; P<0.05), CDK2 (r=−0.799; P<0.05), and CCNE2(r=−0.639; P<0.05) expression in NPC (Fig.…”

The role of prostate tumor overexpressed 1 in cancer progression

“…Very recently, PTOV1 expression was shown to activate Wnt/β-catenin signaling in breast cancer [74]. In the canonical Wnt pathway, binding of Wnt ligand to frizzled receptors and lipoprotein receptor-related protein-5 or 6 (LRP5/6) co-receptors initiates a cascade, which results in β-catenin activation, its nuclear translocation and transcription of target genes [75].…”

“…In human breast carcinoma, high levels of PTOV1 expression correlated with high levels of nuclear β-catenin and low levels of DKK1 [74]. The overexpression of PTOV1 in breast cancer cell lines induced the nuclear translocation of β-catenin and increased β-catenin/TCF transcriptional activity.…”

“…The overexpression of PTOV1 in breast cancer cell lines induced the nuclear translocation of β-catenin and increased β-catenin/TCF transcriptional activity. PTOV1 overexpression repressed DKK1 transcription via the recruitment of HDACs to the promoter and a concomitant decrease of histone acetylation [74]. Treatment with TSA reverted the repression of DKK1 .…”

“…In addition, in breast cancer cells PTOV1 was shown to enhance tumor growth, increase the number of mammospheres, the proportion of the side population (SP), and of CD24 - /CD44 + cells [74]. These findings reveal the ability of the protein PTOV1 to promote CSCs- like properties in cells from different tumor types.…”