Adenomatous polyposis coli (APC)-induced apoptosis of HT29 colorectal cancer cells depends on mitochondrial oxidative metabolism

Maricarmen Cristofaro, Annalisa Contursi, Simona D'Amore, Nicola Martelli, Ada Fiorenza Spaziante, Antonio Moschetta, Gaetano Villani

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Adenomatous polyposis coli (APC) is a tumor suppressor involved in the Wnt signaling, the primary driving force of the intestinal epithelium homeostasis. Alterations of components of the Wnt pathway, and in most cases mutations of APC, have been reported to promote colorectal cancer (CRC). During differentiation the enterocytes migrate from the crypt to the tip of the villus where they undergo apoptosis thus ensuring the continual renewal of the intestinal mucosa. The differentiation process is characterized by an activation gradient of the Wnt signaling pathway accompanied by a metabolic switch from glycolysis to mitochondrial oxidative phosphorylation along the crypt-villus axis. In the present work, we study the relationship between the expression of wild type APC protein and mitochondrial oxidative metabolism in HT29 colorectal cancer cells, originally carrying endogenous inactive APC alleles. By generating mtDNA-depleted (rho0) APC-inducible HT29 cells, we demonstrate for the first time that the APC-dependent apoptosis requires the production of reactive oxygen species (ROS) by the mitochondrial respiratory chain. The possible role of mitochondria as putative target in the prevention and/or therapy of colorectal cancer is herein discussed.

Original languageEnglish (US)
Pages (from-to)1719-1728
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number9
DOIs
StatePublished - Sep 1 2015

Fingerprint

Adenomatous Polyposis Coli
Colorectal Neoplasms
Apoptosis
Wnt Signaling Pathway
Intestinal Mucosa
Adenomatous Polyposis Coli Protein
HT29 Cells
Enterocytes
Oxidative Phosphorylation
Glycolysis
Electron Transport
Mitochondrial DNA
Reactive Oxygen Species
Mitochondria
Homeostasis
Alleles
Mutation
Neoplasms

Keywords

  • Apoptosis
  • Colorectal cancer
  • Mitochondria
  • Reactive oxygen species (ROS)
  • Respiratory chain
  • Wnt signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Adenomatous polyposis coli (APC)-induced apoptosis of HT29 colorectal cancer cells depends on mitochondrial oxidative metabolism. / Cristofaro, Maricarmen; Contursi, Annalisa; D'Amore, Simona; Martelli, Nicola; Spaziante, Ada Fiorenza; Moschetta, Antonio; Villani, Gaetano.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1852, No. 9, 01.09.2015, p. 1719-1728.

Research output: Contribution to journalArticle

Cristofaro, Maricarmen ; Contursi, Annalisa ; D'Amore, Simona ; Martelli, Nicola ; Spaziante, Ada Fiorenza ; Moschetta, Antonio ; Villani, Gaetano. / Adenomatous polyposis coli (APC)-induced apoptosis of HT29 colorectal cancer cells depends on mitochondrial oxidative metabolism. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2015 ; Vol. 1852, No. 9. pp. 1719-1728.
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