title: SOX10 induced Nestin expression regulates cancer stem cell properties of TNBC cells.
abstract: The mechanisms modulating the cancer stem cell (CSC) properties of triple negative breast cancer (TNBC) cells were not fully understood. In this study, we performed data mining in Breast Cancer Gene-Expression Miner v4.0 and found that TNBC tumors had significantly higher NES mRNA expression than other breast cancer subtypes. Pooled data suggested that NES mRNA expression is associated worse metastatic relapse (MR) free survival and also worse any event (AE) free survival in TNBC patients. Following data mining in multiple big data databases confirmed a positive correlation between SOX10 mRNA expression and NES mRNA expression in breast cancer tissues. In addition, the expression of SOX10 mRNA is significantly higher in TNBC tissues than in other breast cancer subtypes. SOX10 overexpression resulted in Nestin upregulation at both mRNA and protein levels. Bioinformatic analysis predicted a SOX10 binding site in NES promoter and the following dual luciferase assay verified the binding site. Functionally, SOX10 overexpression substantially increased CSC properties of TNBC cells, while SOX10 knockdown decreased the CSC properties, in terms of CD24-/CD44+cell ratio and tumorsphere-forming capabilities. Enforced Nestin expression partly counteracted the effect of SOX10 knockdown on reducing the CSC properties. Based on these findings, we infer that SOX10 regulates cancer stem cell properties of TNBC cells via inducing Nestin expression.
authors.affiliation: Department of Oncology, Zaozhuang Mining Group Central Hospital, Zaozhuang 277800, Shandong, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Oncology, Zaozhuang Mining Group Central Hospital, Zaozhuang 277800, Shandong, China. Electronic address: sihailiu@hotmail.com.
authors.forename: Sihai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Oncology, Zaozhuang Mining Group Central Hospital, Zaozhuang 277800, Shandong, China. Electronic address: ruixiazhu@outlook.com.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Zaozhuang Mining Group Central Hospital, Zaozhuang 277800, Shandong, China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Oncology, Zaozhuang Mining Group Central Hospital, Zaozhuang 277800, Shandong, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Zaozhuang Mining Group Central Hospital, Zaozhuang 277800, Shandong, China.
authors.forename: Jinshan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Oncology, Zaozhuang Mining Group Central Hospital, Zaozhuang 277800, Shandong, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Song
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D064231:Nestin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055757:SOXE Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C577484:NES protein, human; D064231:Nestin; D012333:RNA, Messenger; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors
keywords: Cancer stem cell; Nestin; SOX10; TNBC