Source: Xinhua| 2018-04-10 01:36:10|Editor: ZX
WASHINGTON, April 9 (Xinhua) -- American researchers reported on Monday in the journal Cancer Cell that the molecular mechanisms by which fat cells communicate with tumor tissue, providing energy to the latter.
Sanford Prebys Medical Discovery Institute (SBP) researchers elaborated how the metabolism affects tumor formation as obesity is the second-leading preventable cause of cancer.
They found that inactivation of a protein called p62 in fat cells fuels aggressive, metastatic prostate cancer in mice.
The p62 deficiency triggers a shutdown of energy-consuming processes in fat tissue, thereby increasing the availability of nutrients for cancer cells, according to the researchers.
"This work could lead to better therapies that consider cancer not just as a genetic or cellular disease, but as a whole-body process where tumors communicate with metabolic organs to maintain their unlimited appetite for nutrients," said co-senior author Maria Diaz-Meco, a professor in the Cancer Metabolism and Signaling Networks Program at the SBP.
"This is a vulnerability that can be targeted therapeutically," said Diaz-Meco.
Diaz-Meco's team used a mouse model lacking p62 in fat cells, which leads to increased adiposity and metabolic problems.
They found that p62 deficiency in fat cells promotes the progression and metastasis of prostate cancer in mice by inhibiting a protein complex called mTORC1.
The tumors suppress energy-consuming activities such as fat cell development, a metabolic process called oxidative phosphorylation, and fatty acid metabolism in white fat tissue. As a result, more fatty acids and other nutrients are available to support tumor growth.
"This metabolic reprogramming orchestrated by the loss of p62 in adipocytes appears to help tumors cope with the high-energy demands of an aggressive cancer," said Diaz-Meco.
Additional experiments have shown that p62 deficiency in fat tissue promotes the synthesis of proteins called osteopontin and Cpt1a, which are critical for prostate cancer proliferation, migration and invasion.
These findings are clinically relevant because high levels of osteopontin and Cpt1a are associated with aggressive, metastatic castration-resistant prostate cancer in humans.
"The significance is huge because we identify a new set of therapeutic targets that, if modulated, should block the ability of activated adipose tissue to promote tumor malignancy," said the paper's co-auther Jorge Moscat at the SBP.
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