TY - JOUR
AU1 - Wang, Gang
AU2 - Biswas, Anup
AU3 - Ma, Wanchao
AU4 - Kandpal, Manoj
AU5 - Coker, Courtney
AU6 - Grandgenett, Paul
AU7 - Hollingsworth, Michael
AU8 - Jain, Rinku
AU9 - Tanji, Kurenai
AU1 - Lόpez-Pintado, Sara
AU1 - Borczuk, Alain
AU1 - Hebert, Doreen
AU1 - Jenkitkasemwong, Supak
AU1 - Hojyo, Shintaro
AU1 - Davuluri, Ramana
AU1 - Knutson, Mitchell
AU1 - Fukada, Toshiyuki
AU1 - Acharyya, Swarnali
AB - Patients with metastatic cancer experience a severe loss of skeletal muscle mass and function known as cachexia. Cachexia is associated with poor prognosis and accelerated death in patients with cancer, yet its underlying mechanisms remain poorly understood. Here, we identify the metal-ion transporter ZRT- and IRT-like protein 14 (ZIP14) as a critical mediator of cancer-induced cachexia. ZIP14 is upregulated in cachectic muscles of mice and in patients with metastatic cancer and can be induced by TNF-α and TGF-β cytokines. Strikingly, germline ablation or muscle-specific depletion of Zip14 markedly reduces muscle atrophy in metastatic cancer models. We find that ZIP14-mediated zinc uptake in muscle progenitor cells represses the expression of MyoD and Mef2c and blocks muscle-cell differentiation. Importantly, ZIP14-mediated zinc accumulation in differentiated muscle cells 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.
TI - Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle
JF - Nature Medicine
DO - 10.1038/s41591-018-0054-2
DA - 2018-06-06
UR - https://www.deepdyve.com/lp/springer-journals/metastatic-cancers-promote-cachexia-through-zip14-upregulation-in-gyBc58vdOo
SP - 770
EP - 781
VL - 24
IS - 6
DP - DeepDyve
ER -