| RRC ID |
70582
|
| 著者 |
Graca FA, Rai M, Hunt LC, Stephan A, Wang YD, Gordon B, Wang R, Quarato G, Xu B, Fan Y, Labelle M, Demontis F.
|
| タイトル |
The myokine Fibcd1 is an endogenous determinant of myofiber size and mitigates cancer-induced myofiber atrophy.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Decline in skeletal muscle cell size (myofiber atrophy) is a key feature of cancer-induced wasting (cachexia). In particular, atrophy of the diaphragm, the major muscle responsible for breathing, is an important determinant of cancer-associated mortality. However, therapeutic options are limited. Here, we have used Drosophila transgenic screening to identify muscle-secreted factors (myokines) that act as paracrine regulators of myofiber growth. Subsequent testing in mouse myotubes revealed that mouse Fibcd1 is an evolutionary-conserved myokine that preserves myofiber size via ERK signaling. Local administration of recombinant Fibcd1 (rFibcd1) ameliorates cachexia-induced myofiber atrophy in the diaphragm of mice bearing patient-derived melanoma xenografts and LLC carcinomas. Moreover, rFibcd1 impedes cachexia-associated transcriptional changes in the diaphragm. Fibcd1-induced signaling appears to be muscle selective because rFibcd1 increases ERK activity in myotubes but not in several cancer cell lines tested. We propose that rFibcd1 may help reinstate myofiber size in the diaphragm of patients with cancer cachexia.
|
| 巻・号 |
13(1)
|
| ページ |
2370
|
| 公開日 |
2022-5-2
|
| DOI |
10.1038/s41467-022-30120-1
|
| PII |
10.1038/s41467-022-30120-1
|
| PMID |
35501350
|
| PMC |
PMC9061726
|
| MeSH |
Animals
Atrophy / metabolism
Cachexia* / metabolism
Humans
Mice
Muscle Fibers, Skeletal / metabolism
Muscle, Skeletal / metabolism
Neoplasms* / complications
Neoplasms* / genetics
Neoplasms* / metabolism
Receptors, Cell Surface / metabolism
|
| IF |
12.121
|
| リソース情報 |
| ショウジョウバエ |
10593R-1
10593R-3
11062R-1
11062R-2
HMJ21762
9621R-1
9621R-3
HMJ23437
8827R-1
8827R-2
6378R-1
6378R-4
4608R-1
4608R-2
HMJ23358
10186R-1
10186R-4
13830R-1
13830R-3
15537R-1
8343R-1
8343R-2
8483R-1
8483R-3
8642R-1
8642R-2
9400R-2
9400R-4
9849R-1
9849R-2
1869R-1
16987R-1
16987R-2
9885R-1
9885R-2
15388R-3
15388R-4
15537R-2
HMJ30018
17633R-2
17919R-2
12956R-1
17919R-3
1889R-3
HMJ21232
HMJ23751
31999R-1
31999R-4
12956R-3
HMJ30197
5562R-3
HMJ30283
17610R-2
17610R-4
4475R-1
4475R-2
5562R-1
16933R-3
7103R-1
7103R-2
HMC03278
4559R-2
11064R-2
11064R-3
4559R-3
17579R-1
17579R-2
1780R-1
1780R-4
3837R-1
HMJ23141
3837R-9
4700R-1
HMS00476
4700R-2
7532R-1
9027R-2
7532R-3
9027R-4
10334R-2
3074R-1
3322R-2
HMJ23126
6281R-1
3322R-3
6281R-2
6232R-1
6868R-2
6868R-3
HMJ23300
12497R-1
6232R-2
11326R-2
1901R-3
11326R-3
4889R-3
1901R-4
4889R-4
HMJ22320
4698R-2
4698R-3
HMJ22563
6407R-1
4859R-1
4859R-5
HMJ23143
1794-1R-1
1794-1R-2
1838R-1
1838R-3
18657R-1
18657R-2
16933R-1 |
