Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity

Clara Panosa, Francesc Tebar, Montserrat Ferrer-Batallé, Humphrey Fonge, Masaharu Seno, Raymond M. Reilly, Anna Massaguer, Rafael de Llorens

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The members of the epidermal growth factor (EGF)/ErbB family are prime targets for cancer therapy. However, the therapeutic efficiency of the existing anti-ErbB agents is limited. Thus, identifying new molecules that inactivate the ErbB receptors through novel strategies is an important goal on cancer research. In this study we have developed a shorter form of human EGF (EGFt) with a truncated C-terminal as a novel EGFR inhibitor. EGFt was designed based on the superimposition of the three-dimensional structures of EGF and the Potato Carboxypeptidase Inhibitor (PCI), an EGFR blocker previously described by our group. The peptide was produced in E. coli with a high yield of the correctly folded peptide. EGFt showed specificity and high affinity for EGFR but induced poor EGFR homodimerization and phosphorylation. Interestingly, EGFt promoted EGFR internalization and translocation to the cell nucleus although it did not stimulate the cell growth. In addition, EGFt competed with EGFR native ligands, inhibiting the proliferation of cancer cells. These data indicate that EGFt may be a potential EGFR blocker for cancer therapy. In addition, the lack of EGFR-mediated growth-stimulatory activity makes EGFt an excellent delivery agent to target toxins to tumours over-expressing EGFR.

Original languageEnglish
Article numbere69325
JournalPLoS One
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 30 2013

Fingerprint

epidermal growth factor
Epidermal Growth Factor
chemical derivatives
Derivatives
neoplasms
Cells
therapeutics
Carboxypeptidases
Neoplasms
Peptides
Phosphorylation
Cell growth
peptides
carboxypeptidases
Escherichia coli
Tumors
cell nucleus
Ligands
cell growth
phosphorylation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Panosa, C., Tebar, F., Ferrer-Batallé, M., Fonge, H., Seno, M., Reilly, R. M., ... de Llorens, R. (2013). Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity. PLoS One, 8(7), [e69325]. https://doi.org/10.1371/journal.pone.0069325

Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity. / Panosa, Clara; Tebar, Francesc; Ferrer-Batallé, Montserrat; Fonge, Humphrey; Seno, Masaharu; Reilly, Raymond M.; Massaguer, Anna; de Llorens, Rafael.

In: PLoS One, Vol. 8, No. 7, e69325, 30.07.2013.

Research output: Contribution to journalArticle

Panosa, C, Tebar, F, Ferrer-Batallé, M, Fonge, H, Seno, M, Reilly, RM, Massaguer, A & de Llorens, R 2013, 'Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity', PLoS One, vol. 8, no. 7, e69325. https://doi.org/10.1371/journal.pone.0069325
Panosa C, Tebar F, Ferrer-Batallé M, Fonge H, Seno M, Reilly RM et al. Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity. PLoS One. 2013 Jul 30;8(7). e69325. https://doi.org/10.1371/journal.pone.0069325
Panosa, Clara ; Tebar, Francesc ; Ferrer-Batallé, Montserrat ; Fonge, Humphrey ; Seno, Masaharu ; Reilly, Raymond M. ; Massaguer, Anna ; de Llorens, Rafael. / Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity. In: PLoS One. 2013 ; Vol. 8, No. 7.
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