BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript

Bao-Qin Liu; Song Zhang; Si Li; Ming-Xin An; Chao Li; Jing Yan; Jia-Mei Wang; Hua-Qin Wang

doi:10.1038/cddis.2017.324

BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript

Cell Death Dis. 2017 Jul 13;8(7):e2933. doi: 10.1038/cddis.2017.324.

Authors

Bao-Qin Liu^{1

2}, Song Zhang¹, Si Li¹, Ming-Xin An¹, Chao Li¹, Jing Yan¹, Jia-Mei Wang¹, Hua-Qin Wang^{1

2}

Affiliations

¹ Department of Biochemistry &Molecular Biology, China Medical University, Shenyang 110001, China.
² Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.

Abstract

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44⁺/CD24^- CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3'-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer.

MeSH terms

Adaptor Proteins, Signal Transducing / deficiency
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Apoptosis Regulatory Proteins / deficiency
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism*
Benzylamines
Breast Neoplasms / metabolism
Breast Neoplasms / mortality
Breast Neoplasms / pathology*
CRISPR-Cas Systems / genetics
Cell Line, Tumor
Cell Self Renewal
Cyclams
Female
Half-Life
Heterocyclic Compounds / pharmacology
Humans
Kaplan-Meier Estimate
MCF-7 Cells
Nanog Homeobox Protein / genetics
Nanog Homeobox Protein / metabolism
Neoplastic Stem Cells / cytology
Neoplastic Stem Cells / metabolism
Phenotype
Prognosis
Proportional Hazards Models
Receptors, CXCR4 / genetics
Receptors, CXCR4 / metabolism*
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism
Up-Regulation / drug effects

Substances

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
BAG3 protein, human
Benzylamines
CXCR4 protein, human
Cyclams
Heterocyclic Compounds
Nanog Homeobox Protein
Receptors, CXCR4
SOX2 protein, human
SOXB1 Transcription Factors
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