The APC tumor suppressor promotes transcription-independent apoptosis in vitro

Kira Steigerwald, Gregory K. Behbehani, Kelly A. Combs, Michelle Craig Barton, Joanna Groden

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The APC tumor suppressor is found in nonproliferating epithelial cells of the colonic crypts and is mutated in most colorectal tumors. To understand the function of APC in normal epithelium and how its loss leads to tumor formation, we tested whether APC is a mediator of apoptosis using an in vitro assay that monitors caspase-3-mediated cleavage of lamin B protein or a colorimetric substrate in a cell-free Xenopus egg extract. Recombinant APC protein accelerates apoptosis-associated caspase activity independently of ongoing transcription and protein synthesis. Conversely, the addition of mutant APC and immunodepletion of Xenopus APC decelerates apoptosis-associated caspase activity. Acceleration of apoptosis by APC is abolished by the caspase-8 inhibitor Z-IETD-FMK, demonstrating that caspase-8 is an essential component of APC-mediated apoptosis. These results suggest that the induction of apoptosis may be one role of APC in tumor suppression and that this mechanism is independent of β-catenin-mediated effects on transcription.

Original languageEnglish (US)
Pages (from-to)78-89
Number of pages12
JournalMolecular Cancer Research
Volume3
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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