Galectin-3 modulates the EGFR signalling-mediated regulation of Sox2 expression via c-Myc in lung cancer

Hong Yi Kuo, Hsiao Ting Hsu, Yi Chen Chen, Yu Wei Chang, Fu-Tong Liu, Cheng Wen Wu

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalGlycobiology
Volume26
Issue number2
DOIs
StatePublished - May 18 2015

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Keywords

  • c-Myc
  • EGFR
  • galectin-3
  • lung cancer
  • Sox2

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kuo, H. Y., Hsu, H. T., Chen, Y. C., Chang, Y. W., Liu, F-T., & Wu, C. W. (2015). Galectin-3 modulates the EGFR signalling-mediated regulation of Sox2 expression via c-Myc in lung cancer. Glycobiology, 26(2), 155-165. https://doi.org/10.1093/glycob/cwv088