It's estimated that nearly one-third of all cancer deaths are caused not by the cancer itself but by cachexia--a debilitating muscle-wasting syndrome that affects an estimated 80 percent of advanced cancer patients. Cachexia is linked to reduced tolerance for cancer therapy, poor quality of life, and accelerated death, but there are no effective treatments and its cause is still largely unknown.
A new study suggests that an overload of zinc in patients' muscles may be the culprit. The findings, published in Nature Medicine, could pave the way for the development of drugs to treat or prevent muscle wasting in advanced cancer patients.
Cachexia occurs in many types of cancers, including pancreatic, gastrointestinal, lung, and head and neck cancers. Yet the condition remains poorly understood, due in part to limited research funding in this area, difficulty developing animal models that accurately replicate the condition in human cancer, and a lack of reliable biomarkers to help diagnose cachexia early and monitor its progression during cancer treatment.
"There's a common misconception that cachexia is just a nutritional problem caused by a loss of appetite stemming from the cancer or its treatments," says study leader. "Cachectic patients are typically given appetite stimulants, but these remedies only help temporarily and cannot reverse cachexia. As cachexia continues to break down muscle, patients often become too weak to tolerate standard doses of anti-cancer therapies, and their doctors have to scale back treatment. Cachexia can also weaken the muscles of the diaphragm and the heart, causing many cancer patients to die from respiratory or heart failure. To find better ways of treating this condition, we need to learn more about its underlying cause and the molecular mechanisms associated with this syndrome."
In the study, the team looked in the muscles of mice with cachexia to see if they could find differences compared with normal muscles. The analysis revealed greater activity of a protein called ZIP14, which is typically expressed in liver cells to facilitate metal transport but was found to be abnormally expressed in muscles of the cancer models. They also found high levels of ZIP14 in samples of muscle tissue from cancer patients with cachexia, suggesting a link between ZIP14 and cachexia in people.
Excess zinc uptake in muscle leads to muscle wasting in cancer, the researchers found, by breaking down mature muscle cells and preventing stem cells from making new muscle fibers.
The reason why ZIP14 pumps more zinc into muscles in cachexia was traced back to the systemic effects of cancer. The researchers found that two factors--TNF-alpha and TGF-beta, which are associated with advanced cancer--increase ZIP14 expression in muscle.
"We often think cancer injures the body by spreading and invading vital organs," the study lead says. "But cancer can also injure in another way, by releasing substances that affect other areas of the body that are cancer-free. This is an area that is often overlooked in cancer biology research, but addressing it during cancer treatment could have an important impact on patient survival and quality of life."
The discovery of zinc and ZIP14's connection with cachexia may lead to ways to reduce cachexia's impact on patients. In the study, reducing ZIP14 in muscle cells markedly reduced cachexia, suggesting that drugs that inhibit ZIP14 could improve cancer survival and quality of life.
"Zinc is essential for maintaining many functions in our body, and is often taken as a supplement," says the study lead. "But excess zinc supplementation may not always be a good thing, because we saw that giving excess zinc supplements to mice with tumors accelerated their muscle wasting and weight loss. With more translational studies, clinicians and patients may need to reconsider the practice of using zinc supplements, especially if they have tumors commonly associated with cachexia."
http://newsroom.cumc.columbia.edu/blog/2018/06/06/excess-zinc-in-muscles-contributes-to-wasting-syndrome-in-cancer/
https://www.nature.com/articles/s41591-018-0054-2
Latest News
Citrullination is a key pla…
By newseditor
Posted 14 Sep
Senolytic therapy clinical…
By newseditor
Posted 14 Sep
Genetic tools probe microbi…
By newseditor
Posted 13 Sep
A secret passage for mutant…
By newseditor
Posted 11 Sep
Specialized T cells in the…
By newseditor
Posted 10 Sep
Other Top Stories
Nuclear transport protein prevents the aggregation of FUS
Read more
Green tea molecule could prevent heart attacks
Read more
A new twist in transcription!
Read more
Recombinant proteins made from human blood!
Read more
Controlling crowding inside the cell
Read more
Protocols
Genetic manipulation of Pat…
By newseditor
Posted 13 Sep
Single-nucleus RNA sequenci…
By newseditor
Posted 08 Sep
Engineering RNA export for…
By newseditor
Posted 25 Aug
ATP production from electri…
By newseditor
Posted 21 Aug
Labeling PIEZO2 activity in…
By newseditor
Posted 20 Aug
Publications
Timing of lifespan influenc…
By newseditor
Posted 16 Sep
Transformer-based biomarker…
By newseditor
Posted 16 Sep
Somatic variants of MAP3K3…
By newseditor
Posted 16 Sep
The NLRP3 inflammasome and…
By newseditor
Posted 15 Sep
Targeting the metabolism of…
By newseditor
Posted 15 Sep
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar