TY - JOUR
T1 - Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis
AU - Nimri, Lili
AU - Saadi, Janan
AU - Peri, Irena
AU - Yehuda-Shnaidman, Einav
AU - Schwartz, Betty
PY - 2015
Y1 - 2015
N2 - There are an increasing number of reports on obesity being a key risk factor for the development of colon cancer. Our goal in this study was to explore the metabolic networks and molecular signaling pathways linking obesity, adipose tissue and colon cancer. Using in-vivo experiments, we found that mice fed a high-fat diet (HFD) and injected with MC38 colon cancer cells develop significantly larger tumors than their counterparts fed a control diet. In ex-vivo experiments, MC38 and CT26 colon cancer cells exposed to conditioned media (CM) from the adipose tissue of HFD-fed mice demonstrated significantly lower oxygen consumption rate as well as lower maximal oxygen consumption rate after carbonyl cyanide-4-trifluoromethoxy-phenylhydrazone treatment. In addition, in-vitro assays showed downregulated expression of mitochondrial genes in colon cancer cells exposed to CM prepared from the visceral fat of HFD-fed mice or to leptin. Interestingly, leptin levels detected in the media of adipose tissue explants co-cultured with MC38 cancer cells were higher than in adipose tissue explants cultures, indicating cross talk between the adipose tissue and the cancer cells. Salient findings of the present study demonstrate that this crosstalk is mediated at least partially by the JNK/STAT3-signaling pathway.
AB - There are an increasing number of reports on obesity being a key risk factor for the development of colon cancer. Our goal in this study was to explore the metabolic networks and molecular signaling pathways linking obesity, adipose tissue and colon cancer. Using in-vivo experiments, we found that mice fed a high-fat diet (HFD) and injected with MC38 colon cancer cells develop significantly larger tumors than their counterparts fed a control diet. In ex-vivo experiments, MC38 and CT26 colon cancer cells exposed to conditioned media (CM) from the adipose tissue of HFD-fed mice demonstrated significantly lower oxygen consumption rate as well as lower maximal oxygen consumption rate after carbonyl cyanide-4-trifluoromethoxy-phenylhydrazone treatment. In addition, in-vitro assays showed downregulated expression of mitochondrial genes in colon cancer cells exposed to CM prepared from the visceral fat of HFD-fed mice or to leptin. Interestingly, leptin levels detected in the media of adipose tissue explants co-cultured with MC38 cancer cells were higher than in adipose tissue explants cultures, indicating cross talk between the adipose tissue and the cancer cells. Salient findings of the present study demonstrate that this crosstalk is mediated at least partially by the JNK/STAT3-signaling pathway.
KW - Colon cancer
KW - JNK/STAT3
KW - Leptin
KW - Mitochondria
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=84947735795&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.5561
DO - 10.18632/oncotarget.5561
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C2 - 26472027
AN - SCOPUS:84947735795
SN - 1949-2553
VL - 6
SP - 38195
EP - 38209
JO - Oncotarget
JF - Oncotarget
IS - 35
ER -