title: Galectin-3 modulates the EGFR signalling-mediated regulation of Sox2 expression via c-Myc in lung cancer.
abstract: Galectin-3 is a ubiquitous lectin exerting multiple cellular functions such as RNA splicing, protein trafficking and apoptosis. Its expression is positively correlated with the poor prognosis in lung cancer patients. Galectin-3 can promote cancer progression through its effects on cell proliferation, cell survival or cancer metastasis. However, the role of galectin-3 in the regulation of cancer stem-like cells (CSCs) is still unclear. Here, we investigated the hypothesis that galectin-3 might regulate lung CSCs via the EGF receptor (EGFR) signaling pathway. In our study, galectin-3 facilitated EGFR activation and enhanced the sphere formation activity of lung cancer cells. Furthermore, galectin-3 promoted Sox2 expression in an EGFR activation-dependent manner; importantly, forced expression of Sox2 blunted the effect of galectin-3 knockdown on lung cancer sphere formation ability. These results suggest that galectin-3 promotes EGFR activation leading to the upregulation of Sox2 expression and lung CSCs properties. Moreover, we showed that the carbohydrate-binding activity of galectin-3 was important for the regulation of EGFR activation, Sox2 expression and sphere formation. We have recently reported that c-Myc is a transcriptional activator of Sox2. We further found that galectin-3 enhanced c-Myc protein stability leading to increased c-Myc binding to the Sox2 gene promoter. We also examined the effect of the stemness factors, Oct4, Nanog and Sox2 on the expression of galectin-3. We found that Oct4 enhanced galectin-3 expression. Our results together suggest that galectin-3 enhances lung cancer stemness through the EGFR/c-Myc/Sox2 axis; Oct4, in turn, promotes galectin-3 expression, forming a positive regulatory loop in lung CSCs.
authors.affiliation: Institute of Biochemistry and Molecular Biology.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Kuo
authors.affiliation: Institute of Biochemistry and Molecular Biology.
authors.forename: Hsiao-Ting
authors.initials: HT
authors.lastname: Hsu
authors.affiliation: Institute of Biochemistry and Molecular Biology.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Molecular Biology.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan Department of Dermatology, University of California at Davis, Davis, USA.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Molecular Biology Institute of Microbiology and Immunology and Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan cwwu@ym.edu.tw.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D037502:Galectin 3; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D066246:ErbB Receptors
keywords: EGFR; Sox2; c-Myc; galectin-3; lung cancer