title: β-Catenin, a Sox2 binding partner, regulates the DNA binding and transcriptional activity of Sox2 in breast cancer cells.
abstract: Sox2, an embryonic stem cell marker, has been recently implicated in the pathogenesis of breast cancer (BC). Using liquid chromatography-mass spectrometry and co-immunoprecipitation, we identified β-catenin as a Sox2 binding partner in MCF7 cells. The interaction between Sox2 and β-catenin was substantially different between the two cell subsets separated based on their differential responsiveness to a Sox2 reporter. Specifically, while β-catenin binds to Sox2 in the nuclear fraction of cells showing reporter-responsiveness (i.e. RR cells), this interaction was not detectable in those that were reporter-unresponsive (i.e. RU cells). In RR but not in RU cells, siRNA knockdown of β-catenin significantly upregulated the Sox2 transcriptional activity, enhanced its DNA binding and increased the expression of its target genes. Correlating with these findings, while inhibition of β-catenin significantly downregulated the mammosphere formation efficiency in RU cells, this treatment paradoxically increased that of RR cells. To conclude, we identified that β-catenin is an important binding partner of Sox2 and a regulator of its transcriptional activity in a small subset of BC cells. The interaction between Sox2 and β-catenin provides a novel mechanism underlying the functional dichotomy of BC cells, which carries potential therapeutic implications.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Chengsheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Keshav
authors.initials: K
authors.lastname: Gopal
authors.affiliation: Department of Pathology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Yupo
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada; DynaLIFE(DX) Medical Laboratories, Edmonton, AB, Canada. Electronic address: rlai@ualberta.ca.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D011485:Protein Binding; D011794:Quercetin / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics*
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D051176:beta Catenin; D011794:Quercetin
keywords: BC; Breast cancer; LC–MS; Mass spectrometry; RR; RU; Sex determining region Y-Box 2; Sox2; Transcriptional activity; breast cancer; liquid chromatography–mass spectrometry; reporter responsive; reporter unresponsive; β-Catenin