Excess Zinc in Muscles May Drive Cancer-Related Wasting
TUESDAY, Aug. 7, 2018 -- ZRT- and IRT-like protein 14 (ZIP14) upregulation in skeletal muscles may play a role in cancer-related muscle loss, according to a study published online June 6 in Nature Medicine.
Gang Wang, Ph.D., from Columbia University in New York City, and colleagues explored the underlying mechanisms for cachexia (severe loss of skeletal muscle mass and function in metastatic cancer patients), including use of an animal model.
The researchers found that metal-ion transporter ZIP14 is a critical mediator of cancer-induced cachexia. In cachectic muscles of mice and in patients with metastatic cancer, ZIP14 is upregulated and can be induced by tumor necrosis factor (TNF)-α and TGF-β cytokines. There is marked reduction in muscle atrophy in metastatic cancer models with germline ablation or muscle-specific depletion of Zip14. ZIP14-mediated zinc uptake in muscle progenitor cells represses the expression of MyoD and Mef2c and blocks muscle-cell differentiation. In differentiated muscle cells, ZIP14-mediated zinc accumulation induces myosin heavy chain loss.
"These results highlight a previously unrecognized role for altered zinc homeostasis in metastatic cancer-induced muscle wasting and implicate ZIP14 as a therapeutic target for its treatment," the authors write.
Posted: August 2018