Abstract
Malignancy is a manifestation of acquired defects in regulatory circuits that direct normal cell proliferation and homeostasis. Most of these circuits operate through cell autonomous pathways, whereas others potentially involve the neighboring microenvironment. We report that the metalloprotease ADAM17 plays a pivotal role in several acquired tumor cell capabilities by mediating the availability of soluble transforming growth factor-α, an epidermal growth factor receptor (EGFR) ligand, and thus the establishment of a key autocrine signaling pathway. Silencing of ADAM17 in human renal carcinoma cell lines corrects critical features associated with cancer cells, including growth autonomy, tumor inflammation, and tissue invasion. Highly malignant renal carcinoma cancer cells fail to form in vivo tumors in the absence of ADAM17, confirming the essential function of this molecule in tumorigenesis. These data show that ligand shedding is a crucial step in endogenous EGFR activation and endorse prospective therapeutic strategies targeting ADAM17 in human cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 8083-8090 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 66 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 15 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17. / Franovic, Aleksandra; Robert, Isabelle; Smith, Karlene; Kurban, Ghada; Pause, Arnim; Gunaratnam, Lakshman; Lee, Stephen.
In: Cancer Research, Vol. 66, No. 16, 15.08.2006, p. 8083-8090.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17
AU - Franovic, Aleksandra
AU - Robert, Isabelle
AU - Smith, Karlene
AU - Kurban, Ghada
AU - Pause, Arnim
AU - Gunaratnam, Lakshman
AU - Lee, Stephen
PY - 2006/8/15
Y1 - 2006/8/15
N2 - Malignancy is a manifestation of acquired defects in regulatory circuits that direct normal cell proliferation and homeostasis. Most of these circuits operate through cell autonomous pathways, whereas others potentially involve the neighboring microenvironment. We report that the metalloprotease ADAM17 plays a pivotal role in several acquired tumor cell capabilities by mediating the availability of soluble transforming growth factor-α, an epidermal growth factor receptor (EGFR) ligand, and thus the establishment of a key autocrine signaling pathway. Silencing of ADAM17 in human renal carcinoma cell lines corrects critical features associated with cancer cells, including growth autonomy, tumor inflammation, and tissue invasion. Highly malignant renal carcinoma cancer cells fail to form in vivo tumors in the absence of ADAM17, confirming the essential function of this molecule in tumorigenesis. These data show that ligand shedding is a crucial step in endogenous EGFR activation and endorse prospective therapeutic strategies targeting ADAM17 in human cancer.
AB - Malignancy is a manifestation of acquired defects in regulatory circuits that direct normal cell proliferation and homeostasis. Most of these circuits operate through cell autonomous pathways, whereas others potentially involve the neighboring microenvironment. We report that the metalloprotease ADAM17 plays a pivotal role in several acquired tumor cell capabilities by mediating the availability of soluble transforming growth factor-α, an epidermal growth factor receptor (EGFR) ligand, and thus the establishment of a key autocrine signaling pathway. Silencing of ADAM17 in human renal carcinoma cell lines corrects critical features associated with cancer cells, including growth autonomy, tumor inflammation, and tissue invasion. Highly malignant renal carcinoma cancer cells fail to form in vivo tumors in the absence of ADAM17, confirming the essential function of this molecule in tumorigenesis. These data show that ligand shedding is a crucial step in endogenous EGFR activation and endorse prospective therapeutic strategies targeting ADAM17 in human cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=33748037366&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-1595
DO - 10.1158/0008-5472.CAN-06-1595
M3 - Article
VL - 66
SP - 8083
EP - 8090
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 16
ER -