TY - JOUR
T1 - Bax is necessary for PGC1α pro-apoptotic effect in colorectal cancer cells
AU - D'Errico, Ilenia
AU - Lo Sasso, Giuseppe
AU - Salvatore, Lorena
AU - Murzilli, Stefania
AU - Martelli, Nicola
AU - Cristofaro, Maricarmen
AU - Latorre, Dominga
AU - Villani, Gaetano
AU - Moschetta, Antonio
PY - 2011/9/1
Y1 - 2011/9/1
N2 - We have recently shown that the transcriptional coactivator PGC1α, a master regulator of mitochondrial biogenesis and function, is involved in the control of the intestinal epithelium cell fate. Furthermore, PGC1α protects against colon cancer formation by promoting ROS accumulation and, consequently, mitochondria-mediated apoptosis. Here we provide an additional mechanistic insight into the tumor suppressor activity of PGC1α showing that its pro-apoptotic effect is mediated by Bax. In fact, PGC1α overexpression in HCT116 Bax -/- colorectal cancer cells stimulates mitochondrial production and activity, but it fails to induce cell death as well as to oppose tumor growth in the xenograft model. The lack of ROS accumulation in the Bax -/- cells strengthens our view that the PGC1α-induced oxidative burst represents one of the main apoptosis-driving factors in colorectal cancer cells.
AB - We have recently shown that the transcriptional coactivator PGC1α, a master regulator of mitochondrial biogenesis and function, is involved in the control of the intestinal epithelium cell fate. Furthermore, PGC1α protects against colon cancer formation by promoting ROS accumulation and, consequently, mitochondria-mediated apoptosis. Here we provide an additional mechanistic insight into the tumor suppressor activity of PGC1α showing that its pro-apoptotic effect is mediated by Bax. In fact, PGC1α overexpression in HCT116 Bax -/- colorectal cancer cells stimulates mitochondrial production and activity, but it fails to induce cell death as well as to oppose tumor growth in the xenograft model. The lack of ROS accumulation in the Bax -/- cells strengthens our view that the PGC1α-induced oxidative burst represents one of the main apoptosis-driving factors in colorectal cancer cells.
KW - Apoptosis
KW - Intestine
KW - Mitochondria
KW - Nuclear receptors
KW - Reactive oxygen species (ROS)
UR - http://www.scopus.com/inward/record.url?scp=80052400864&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052400864&partnerID=8YFLogxK
U2 - 10.4161/cc.10.17.16791
DO - 10.4161/cc.10.17.16791
M3 - Article
C2 - 21862870
AN - SCOPUS:80052400864
VL - 10
SP - 2937
EP - 2945
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 17
ER -