EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis

Y. Feng, X. Dai, X. Li, H. Wang, J. Liu, J. Zhang, Y. Du, L. Xia

Research output: Contribution to journalArticle

Abstract

Objectives: Cancer stem cells (CSCs) compose a subpopulation of cells within a tumour that can self-renew and proliferate. Growth factors such as epidermal growth factor (EGF) and basic fibroblast growth factor (b-FGF) promote cancer stem cell proliferation in many solid tumours. This study assesses whether EGF, bFGF and IGF signalling pathways are essential for colon CSC proliferation and self-renewal. Material and methods: Colon CSCs were cultured in serum-free medium (SFM) with one of the following growth factors: EGF, bFGF or IGF. Characteristics of CSC gene expression were evaluated by real time PCR. Tumourigenicity of CSCs was determined using a xenograft model in vivo. Effects of EGF receptor inhibitors, Gefitinib and PD153035, on CSC proliferation, apoptosis and signalling were evaluated using fluorescence-activated cell sorting and western blotting. Results: Colon cancer cell HCT116 transformed to CSCs in SFM. Compared to other growth factors, EGF was essential to support proliferation of CSCs that expressed higher levels of progenitor genes (Musashi-1, LGR5) and lower levels of differential genes (CK20). CSCs promoted more rapid tumour growth than regular cancer cells in xenografts. EGFR inhibitors suppressed proliferation and induced apoptosis of CSCs by inhibiting autophosphorylation of EGFR and downstream signalling proteins, such as Akt kinase, extracellular signal-regulated kinase 1/2 (ERK 1/2). Conclusions: This study indicates that EGF signalling was essential for formation and maintenance of colon CSCs. Inhibition of the EGF signalling pathway may provide a useful strategy for treatment of colon cancer.

Original languageEnglish (US)
Pages (from-to)413-419
Number of pages7
JournalCell Proliferation
Volume45
Issue number5
DOIs
StatePublished - Oct 2012
Externally publishedYes

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Neoplastic Stem Cells
Epidermal Growth Factor
Colonic Neoplasms
Cell Proliferation
Apoptosis
Intercellular Signaling Peptides and Proteins
Serum-Free Culture Media
Heterografts
Neoplasms
HCT116 Cells
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Fibroblast Growth Factor 2
Epidermal Growth Factor Receptor
Genes
Real-Time Polymerase Chain Reaction
Flow Cytometry
Phosphotransferases
Western Blotting
Maintenance

ASJC Scopus subject areas

  • Cell Biology

Cite this

EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis. / Feng, Y.; Dai, X.; Li, X.; Wang, H.; Liu, J.; Zhang, J.; Du, Y.; Xia, L.

In: Cell Proliferation, Vol. 45, No. 5, 10.2012, p. 413-419.

Research output: Contribution to journalArticle

Feng, Y, Dai, X, Li, X, Wang, H, Liu, J, Zhang, J, Du, Y & Xia, L 2012, 'EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis', Cell Proliferation, vol. 45, no. 5, pp. 413-419. https://doi.org/10.1111/j.1365-2184.2012.00837.x
Feng, Y. ; Dai, X. ; Li, X. ; Wang, H. ; Liu, J. ; Zhang, J. ; Du, Y. ; Xia, L. / EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis. In: Cell Proliferation. 2012 ; Vol. 45, No. 5. pp. 413-419.
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