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TACE is required for the activation of the EGFR by TGF‐α in tumors
Author(s) -
BorrellPagès Maria,
Rojo Federico,
Albanell Joan,
Baselga Josep,
Arribas Joaquín
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg111
Subject(s) - tgf alpha , epidermal growth factor receptor , transmembrane protein , transforming growth factor , cancer research , receptor , carcinogenesis , in vivo , epidermal growth factor , growth factor receptor inhibitor , biology , protease , microbiology and biotechnology , medicine , cancer , enzyme , biochemistry
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.