Potential for modulation of the Fas apoptotic pathway by epidermal growth factor in sarcomas

David E. Joyner, Kevin B. Jones, Stephen L. Lessnick, Joshua D. Schiffman, R Randall

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

One important mechanism by which cancer cells parasitize their host is by escaping apoptosis. Thus, selectively facilitating apoptosis is a therapeutic mechanism by which oncotherapy may prove highly advantageous. One major apoptotic pathway is mediated by Fas ligand (FasL). The death-inducing signaling Ccmplex (DISC) and subsequent death-domain aggregations are created when FasL is bound by its receptor thereby enabling programmed cell death. Conceptually, if a better understanding of the Fas pathway can be garnered, an oncoselective prodeath therapeutic approach can be tailored. Herein, we propose that EGF and CTGF play essential roles in the regulation of the Fas apoptotic pathway in sarcomas. Tumor and in vitro data suggest viable cells counter the prodeath signal induced by FasL by activating EGF, which in turn induces prosurvival CTGF. The prosurvival attributes of CTGF ultimately predominate over the death-inducing FasL. Cells destined for elimination inhibit this prosurvival response via a presently undefined pathway. This scenario represents a novel role for EGF and CTGF as regulators of the Fas pathway in sarcomas.

Original languageEnglish (US)
Article number847409
JournalSarcoma
Volume2011
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

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Fas Ligand Protein
Epidermal Growth Factor
Sarcoma
Apoptosis
Neoplasms
Cell Death
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Potential for modulation of the Fas apoptotic pathway by epidermal growth factor in sarcomas. / Joyner, David E.; Jones, Kevin B.; Lessnick, Stephen L.; Schiffman, Joshua D.; Randall, R.

In: Sarcoma, Vol. 2011, 847409, 01.12.2011.

Research output: Contribution to journalArticle

Joyner, David E. ; Jones, Kevin B. ; Lessnick, Stephen L. ; Schiffman, Joshua D. ; Randall, R. / Potential for modulation of the Fas apoptotic pathway by epidermal growth factor in sarcomas. In: Sarcoma. 2011 ; Vol. 2011.
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