Advertisement

TACE is required for the activation of the EGFR by TGF‐α in tumors

Maria Borrell‐Pagès, Federico Rojo, Joan Albanell, Josep Baselga, Joaquín Arribas

Author Affiliations

  1. Maria Borrell‐Pagès1,
  2. Federico Rojo1,
  3. Joan Albanell2,
  4. Josep Baselga1 and
  5. Joaquín Arribas*,1
  1. 1 Laboratori de Recerca Oncològica, Servei d'Oncologia Medica, Hospital Universitari Vall d'Hebron, Psg. Vall d'Hebron 119–129, Barcelona, 08035, Spain
  2. 2 Present address: Servei d'Oncologia Medica, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
  1. *Corresponding author. E-mail: jarribas{at}hg.vhebron.es
View Full Text

Abstract

The factors and mechanisms that transduce the intracellular signals sent upon activation of the receptor for the epidermal growth factor (EGFR) and related receptors are reasonably well understood and, in fact, are the targets of anti‐tumor drugs. In contrast, less is known about the mechanisms implicated in sending the signals that activate these receptors. Here we show that when its proteolytic shedding is prevented, the transmembrane form of the transforming growth factor‐α (proTGF‐α) interacts with, but does not activate, the EGFR. Thus, shedding seems to control not only the availability of the soluble form of the growth factor (TGF‐α) but also the activity of the transmembrane form. The activity of the protease responsible for the shedding of proTGF‐α, tumor necrosis factor‐α converting enzyme (TACE), is required for the activation of the EGFR in vivo and for the development of tumors in nude mice, indicating a crucial role of TACE in tumorigenesis. In agreement with this view, TACE is dramatically overexpressed in the majority of mammary tumors analyzed. Collectively, this evidence points to TACE as a promising target of anti‐tumor therapy.

  • Received May 29, 2002.
  • Revision received November 8, 2002.
  • Accepted January 14, 2003.
View Full Text