TY - JOUR
T1 - Adenomatous polyposis coli (APC)-induced apoptosis of HT29 colorectal cancer cells depends on mitochondrial oxidative metabolism
AU - Cristofaro, Maricarmen
AU - Contursi, Annalisa
AU - D'Amore, Simona
AU - Martelli, Nicola
AU - Spaziante, Ada Fiorenza
AU - Moschetta, Antonio
AU - Villani, Gaetano
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Colorectal cancer
KW - Mitochondria
KW - Reactive oxygen species (ROS)
KW - Respiratory chain
KW - Wnt signaling
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UR - http://www.scopus.com/inward/citedby.url?scp=84930650009&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2015.05.009
DO - 10.1016/j.bbadis.2015.05.009
M3 - Article
C2 - 26004395
AN - SCOPUS:84930650009
SN - 0925-4439
VL - 1852
SP - 1719
EP - 1728
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 9
ER -