Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17

Aleksandra Franovic, Isabelle Robert, Karlene Smith, Ghada Kurban, Arnim Pause, Lakshman Gunaratnam, Stephen Lee

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)8083-8090
Number of pages8
JournalCancer Research
Volume66
Issue number16
DOIs
StatePublished - Aug 15 2006
Externally publishedYes

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Carcinoma
Kidney
Neoplasms
Renal Cell Carcinoma
Epidermal Growth Factor Receptor
Autocrine Communication
Ligands
Transforming Growth Factors
Metalloproteases
ADAM17 Protein
Carcinogenesis
Homeostasis
Cell Proliferation
Inflammation
Cell Line
Growth
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Franovic, A., Robert, I., Smith, K., Kurban, G., Pause, A., Gunaratnam, L., & Lee, S. (2006). Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17. Cancer Research, 66(16), 8083-8090. https://doi.org/10.1158/0008-5472.CAN-06-1595

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 journalArticle

Franovic, A, Robert, I, Smith, K, Kurban, G, Pause, A, Gunaratnam, L & Lee, S 2006, 'Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17', Cancer Research, vol. 66, no. 16, pp. 8083-8090. https://doi.org/10.1158/0008-5472.CAN-06-1595
Franovic A, Robert I, Smith K, Kurban G, Pause A, Gunaratnam L et al. Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17. Cancer Research. 2006 Aug 15;66(16):8083-8090. https://doi.org/10.1158/0008-5472.CAN-06-1595
Franovic, Aleksandra ; Robert, Isabelle ; Smith, Karlene ; Kurban, Ghada ; Pause, Arnim ; Gunaratnam, Lakshman ; Lee, Stephen. / Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17. In: Cancer Research. 2006 ; Vol. 66, No. 16. pp. 8083-8090.
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