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Proteomics analysis of C2C12 myotubes treated with atrophy inducing cancer cell-derived factors
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  • Akbar Marzan,
  • Sai Chitti,
  • Sriram Gummadi,
  • Taeyoung Kang,
  • Ching-Seng Ang,
  • Suresh Mathivanan
Akbar Marzan
La Trobe University La Trobe Institute for Molecular Science
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Sai Chitti
La Trobe University
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Sriram Gummadi
La Trobe University
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Taeyoung Kang
La Trobe University
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Ching-Seng Ang
University of Melbourne Faculty of Veterinary and Agricultural Sciences
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Suresh Mathivanan
La Trobe University

Corresponding Author:[email protected]

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Cancer-associated cachexia is a wasting syndrome that results in dramatic loss of whole-body weight, predominantly due to loss of skeletal muscle mass. It has been established that cachexia inducing cancer cells secrete proteins and extracellular vesicles (EVs) that can induce muscle atrophy. Though several studies examined these cancer-cell derived factors, targeting some of these components have shown little or no clinical benefit. To develop new therapies, understanding of the dysregulated proteins and signalling pathways that regulate catabolic gene expression during muscle wasting is essential. Here, we sought to examine the effect of conditioned media (CM) that contain secreted factors and EVs from cachexia inducing C26 colon cancer cells on C2C12 myotubes using mass spectrometry-based label-free quantitative proteomics. We identified significant changes in the protein profile of C2C12 cells upon exposure to C26-derived CM. Functional enrichment analysis revealed enrichment of proteins associated with inflammation, mitochondrial dysfunction, muscle catabolism, ROS production, and ER stress in CM treated myotubes. Furthermore, strong downregulation in muscle structural integrity and development and/or regenerative pathways were observed. Together, these enriched proteins in atrophied muscle could be utilized as potential muscle wasting markers and the dysregulated biological processes could be employed for therapeutic benefit in cancer-induced muscle wasting.
23 Jun 2023Submitted to PROTEOMICS
30 Jun 2023Assigned to Editor
30 Jun 2023Submission Checks Completed
30 Jun 2023Review(s) Completed, Editorial Evaluation Pending
10 Jul 2023Reviewer(s) Assigned
18 Aug 2023Editorial Decision: Revise Minor
16 Oct 2023Review(s) Completed, Editorial Evaluation Pending
16 Oct 2023Editorial Decision: Accept