Catabolism of skeletal muscle in cachexia (WP5474)

Homo sapiens

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Cancer related cachexia is a metabolic disease that is defined by an increased breakdown of muscle protein. Muscle breakdown in cachexia occurs mostly due to activation of either the ubiquitin proteasome system, or the autophagy lysosomal system. In this pathway an overview is presented of the different mechanisms that have been found to activate these two systems involved in muscle degradation.

Authors

Nberk , Eric Weitz , and Egon Willighagen

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Disease Ontology

cancer

Pathway Ontology

signaling pathway disease pathway cancer pathway

Cell Type Ontology

muscle cell cell of skeletal muscle

Participants
Query Drugst.One

Label Type Compact URI Comment
IL6 GeneProduct ensembl:ENSG00000136244
NFKBIA GeneProduct ensembl:ENSG00000100906
IL1A GeneProduct ensembl:ENSG00000115008
STAT3 GeneProduct ensembl:ENSG00000168610
MTOR GeneProduct ensembl:ENSG00000198793
MAP1LC3A GeneProduct ensembl:ENSG00000101460
IGF1R GeneProduct ensembl:ENSG00000140443
IGF1 GeneProduct ensembl:ENSG00000017427
RPTOR GeneProduct ensembl:ENSG00000141564
AKT1 GeneProduct ensembl:ENSG00000142208
SMAD2 GeneProduct ensembl:ENSG00000175387
TNFRSF1A GeneProduct ensembl:ENSG00000067182
JAK1 GeneProduct ensembl:ENSG00000162434
FOXO3 GeneProduct ensembl:ENSG00000118689
REL GeneProduct ensembl:ENSG00000162924
NFKB1 GeneProduct ensembl:ENSG00000109320
NFKB2 GeneProduct ensembl:ENSG00000077150
IL1R1 GeneProduct ensembl:ENSG00000115594
PI3K GeneProduct pfam:PF00454
RELA GeneProduct ensembl:ENSG00000173039
ACVR2A GeneProduct ensembl:ENSG00000121989
IL1B GeneProduct ensembl:ENSG00000125538
SMAD3 GeneProduct ensembl:ENSG00000166949
MLST8 GeneProduct ensembl:ENSG00000167965
PDK1 GeneProduct ensembl:ENSG00000152256
TNFRSF12A GeneProduct ensembl:ENSG00000006327
IKBKG GeneProduct ensembl:ENSG00000269335
RELB GeneProduct ensembl:ENSG00000104856
AKT1S1 GeneProduct ensembl:ENSG00000204673
IKBKB GeneProduct ensembl:ENSG00000104365
TNFSF12 GeneProduct ensembl:ENSG00000239697
SMAD4 GeneProduct ensembl:ENSG00000141646
MSTN GeneProduct ensembl:ENSG00000138379
IL6R GeneProduct ensembl:ENSG00000160712
CHUK GeneProduct ensembl:ENSG00000213341
TNF GeneProduct ensembl:ENSG00000232810
FBXO32 GeneProduct ensembl:ENSG00000156804 atrogin-1/MAFbx
TRIM63 GeneProduct ensembl:ENSG00000158022 MuRF1
CEBPB GeneProduct ensembl:ENSG00000172216
MAPK11 GeneProduct ensembl:ENSG00000185386 p38beta MAPK
EP300 Protein ensembl:ENSG00000100393
TRIM63 Protein ensembl:ENSG00000158022
FBXO32 Protein ensembl:ENSG00000156804
MAP1LC3A Protein ensembl:ENSG00000101460

References

  1. NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes. Li YP, Reid MB. Am J Physiol Regul Integr Comp Physiol. 2000 Oct;279(4):R1165-70. PubMed Europe PMC Scholia
  2. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14440–5. PubMed Europe PMC Scholia
  3. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, et al. Cell. 2004 Apr 30;117(3):399–412. PubMed Europe PMC Scholia
  4. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HGW, et al. Cell. 2004 Oct 15;119(2):285–98. PubMed Europe PMC Scholia
  5. The myostatin gene: physiology and pharmacological relevance. Joulia-Ekaza D, Cabello G. Curr Opin Pharmacol. 2007 Jun;7(3):310–5. PubMed Europe PMC Scholia
  6. FoxO3 controls autophagy in skeletal muscle in vivo. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, et al. Cell Metab. 2007 Dec;6(6):458–71. PubMed Europe PMC Scholia
  7. How the Smads regulate transcription. Ross S, Hill CS. Int J Biochem Cell Biol. 2008;40(3):383–408. PubMed Europe PMC Scholia
  8. Mechanisms regulating skeletal muscle growth and atrophy. Schiaffino S, Dyar KA, Ciciliot S, Blaauw B, Sandri M. FEBS J. 2013 Sep;280(17):4294–314. PubMed Europe PMC Scholia
  9. Smad3 induces atrogin-1, inhibits mTOR and protein synthesis, and promotes muscle atrophy in vivo. Goodman CA, McNally RM, Hoffmann FM, Hornberger TA. Mol Endocrinol. 2013 Nov;27(11):1946–57. PubMed Europe PMC Scholia
  10. Role of the TWEAK-Fn14-cIAP1-NF-κB Signaling Axis in the Regulation of Myogenesis and Muscle Homeostasis. Enwere EK, Lacasse EC, Adam NJ, Korneluk RG. Front Immunol. 2014 Feb 5;5:34. PubMed Europe PMC Scholia
  11. STAT3 promotes IFNγ/TNFα-induced muscle wasting in an NF-κB-dependent and IL-6-independent manner. Ma JF, Sanchez BJ, Hall DT, Tremblay AMK, Di Marco S, Gallouzi IE. EMBO Mol Med. 2017 May;9(5):622–37. PubMed Europe PMC Scholia
  12. Recent advances in understanding the role of FOXO3. Stefanetti RJ, Voisin S, Russell A, Lamon S. F1000Res. 2018 Aug 31;7:F1000 Faculty Rev-1372. PubMed Europe PMC Scholia
  13. MuRF1/TRIM63, Master Regulator of Muscle Mass. Peris-Moreno D, Taillandier D, Polge C. Int J Mol Sci. 2020 Sep 11;21(18):6663. PubMed Europe PMC Scholia
  14. Weight Loss in Cancer Patients Correlates With p38β MAPK Activation in Skeletal Muscle. Zhang G, Anderson LJ, Gao S, Sin TK, Zhang Z, Wu H, et al. Front Cell Dev Biol. 2021 Dec 7;9:784424. PubMed Europe PMC Scholia
  15. Interleukin-1 and Nuclear Factor Kappa B Signaling Promote Breast Cancer Progression and Treatment Resistance. Diep S, Maddukuri M, Yamauchi S, Geshow G, Delk NA. Cells. 2022 May 18;11(10):1673. PubMed Europe PMC Scholia
  16. STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20. Antonia RJ, Karelehto E, Toriguchi K, Matli M, Warren RS, Pfeffer LM, et al. J Cell Mol Med. 2022 Aug;26(16):4591–601. PubMed Europe PMC Scholia