Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth.
Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth.
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DOI：
10.1038/s42003-023-04902-2
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发表时间：
2023-05-13
影响因子：
5.9
通讯作者：
Judge, Andrew R.
中科院分区：
文献类型：
--
作者：
Neyroud, Daria;Laitano, Orlando;Dasgupta, Aneesha;Lopez, Christopher;Schmitt, Rebecca E.;Schneider, Jessica Z.;Hammers, David W.;Sweeney, H. Lee;Walter, Glenn A.;Doles, Jason;Judge, Sarah M.;Judge, Andrew R.
癌症引起的肌肉萎缩降低生活质量，使癌症治疗复杂化或排除癌症治疗，并预测早期死亡率。在此，我们研究了肌肉特异性E3泛素连接酶MuRF 1对胰腺癌诱导的肌肉萎缩的需求。将鼠胰腺癌（KPC）细胞或盐水注射到WT和MuRF 1-/-小鼠的胰腺中，并在整个肿瘤进展过程中分析组织。KPC肿瘤在WT小鼠中诱导骨骼肌进行性消耗和全身代谢重编程，但在MuRF 1-/-小鼠中不诱导。来自MuRF 1-/-小鼠的KPC肿瘤也生长较慢，并且显示出通常被快速生长的肿瘤耗尽的代谢物的积累。从机制上讲，MuRF 1是KPC诱导的细胞骨架和肌肉收缩蛋白泛素化增加以及支持蛋白质合成的蛋白质抑制所必需的。总之，这些数据表明，MuRF 1是KPC诱导的骨骼肌萎缩所必需的，其缺失会重新编程全身和肿瘤代谢组并延迟肿瘤生长。整合的体内蛋白质组、泛素组和代谢组分析表征了E3泛素连接酶MuRF 1/Trim 63在肌肉萎缩和胰腺肿瘤生长之间的相互作用中所起的关键作用。
Cancer-induced muscle wasting reduces quality of life, complicates or precludes cancer treatments, and predicts early mortality. Herein, we investigate the requirement of the muscle-specific E3 ubiquitin ligase, MuRF1, for muscle wasting induced by pancreatic cancer. Murine pancreatic cancer (KPC) cells, or saline, were injected into the pancreas of WT and MuRF1-/- mice, and tissues analyzed throughout tumor progression. KPC tumors induces progressive wasting of skeletal muscle and systemic metabolic reprogramming in WT mice, but not MuRF1-/- mice. KPC tumors from MuRF1-/- mice also grow slower, and show an accumulation of metabolites normally depleted by rapidly growing tumors. Mechanistically, MuRF1 is necessary for the KPC-induced increases in cytoskeletal and muscle contractile protein ubiquitination, and the depression of proteins that support protein synthesis. Together, these data demonstrate that MuRF1 is required for KPC-induced skeletal muscle wasting, whose deletion reprograms the systemic and tumor metabolome and delays tumor growth. Integrated in vivo proteome, ubiquitinome, and metabolome profiling characterizes the crucial role played by the E3 ubiquitin ligase MuRF1/Trim63 in the cross-talk between muscle wasting and pancreatic tumor growth.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
DOI：
10.1002/jcsm.12354
发表时间：
2018-10
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Brown JL;Lee DE;Rosa-Caldwell ME;Brown LA;Perry RA;Haynie WS;Huseman K;Sataranatarajan K;Van Remmen H;Washington TA;Wiggs MP;Greene NP
通讯作者：
Greene NP
影响因子：
11
作者：
Beloborodova N;Bairamov I;Olenin A;Shubina V;Teplova V;Fedotcheva N
通讯作者：
Fedotcheva N
影响因子：
14.9
作者：
Deutsch EW;Csordas A;Sun Z;Jarnuczak A;Perez-Riverol Y;Ternent T;Campbell DS;Bernal-Llinares M;Okuda S;Kawano S;Moritz RL;Carver JJ;Wang M;Ishihama Y;Bandeira N;Hermjakob H;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
8.9
作者：
Adams, Volker;Bowen, T. Scott;Labeit, Siegfried
通讯作者：
Labeit, Siegfried