Grb7, a Critical Mediator of EGFR/ErbB Signaling, in Cancer Development and as a Potential Therapeutic Target

Cells. 2019 May 10;8(5):435. doi: 10.3390/cells8050435.

Abstract

The partner of activated epidermal growth factor receptor (EGFR), growth factor receptor bound protein-7 (Grb7), a functionally multidomain adaptor protein, has been demonstrated to be a pivotal regulator for varied physiological and pathological processes by interacting with phospho-tyrosine-related signaling molecules to affect the transmission through a number of signaling pathways. In particular, critical roles of Grb7 in erythroblastic leukemia viral oncogene homolog (ERBB) family-mediated cancer development and malignancy have been intensively evaluated. The overexpression of Grb7 or the coamplification/cooverexpression of Grb7 and members of the ERBB family play essential roles in advanced human cancers and are associated with decreased survival and recurrence of cancers, emphasizing Grb7's value as a prognostic marker and a therapeutic target. Peptide inhibitors of Grb7 are being tested in preclinical trials for their possible therapeutic effects. Here, we review the molecular, functional, and clinical aspects of Grb7 in ERBB family-mediated cancer development and malignancy with the aim to reveal alternative and effective therapeutic strategies.

Keywords: ERBB family; cancer development; epidermal growth factor receptor; growth factor receptor bound protein-7; prognostic marker; therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor* / chemistry
  • Biomarkers, Tumor* / metabolism
  • Biomarkers, Tumor* / physiology
  • ErbB Receptors / metabolism
  • GRB7 Adaptor Protein* / chemistry
  • GRB7 Adaptor Protein* / metabolism
  • GRB7 Adaptor Protein* / physiology
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / therapy
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • GRB7 protein, human
  • GRB7 Adaptor Protein
  • EGFR protein, human
  • ErbB Receptors