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Acquired Capabilities of Cancer Cells Intersect at ADAM17 (TACE)
Author(s) -
Franovic Aleksandra,
Lee Stephen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb72-c
Subject(s) - autocrine signalling , gene silencing , epidermal growth factor receptor , cancer research , cancer cell , cancer , biology , epidermal growth factor , microbiology and biotechnology , receptor , biochemistry , genetics , gene
Autocrine signalling is a key feature in human cancer that allows tumour cells to proliferate and invade surrounding tissues independent of external cues. Here we demonstrate that the stable silencing of a single protease, ADAM17, is sufficient to abrogate several malignant phenotypes in clear cell renal carcinoma (RCC), a highly invasive human cancer. Silencing ADAM17 limits the availability of soluble transforming growth factor‐alpha (TGFα), an epidermal growth factor receptor (EGFR) ligand, thereby preventing EGFR activation and the establishment of this autocrine growth stimulatory loop. Moreover, inhibiting ADAM17 impedes tumour inflammation, survival, migration and invasion, and abolishes tumour formation in vivo . These data show that ligand‐shedding is a critical step in EGFR activation and they reveal that targeting one biologically relevant enzyme is sufficient to abrogate several fundamental tumour‐promoting features. The full therapeutic consequence of targeting ADAM17 in the treatment of cancer will be discussed here.