title: EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: X
authors.initials: X
authors.lastname: Dai
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.forename: L
authors.initials: L
authors.lastname: Xia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000502:physiology*; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D004815:Epidermal Growth Factor; D000077156:Gefitinib