[Retracted] Myostatin is a novel tumoral factor that induces cancer cachexia
Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of infor...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/98861 http://hdl.handle.net/10220/12677 |
| _version_ | 1826111277161775104 |
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| author | Lokireddy, Sudarsanareddy Wijesoma, Isuru Wijerupage Bonala, Sabeera Wei, Meng Sze, Siu Kwan McFarlane, Craig Kambadur, Ravi Sharma, Mridula |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Lokireddy, Sudarsanareddy Wijesoma, Isuru Wijerupage Bonala, Sabeera Wei, Meng Sze, Siu Kwan McFarlane, Craig Kambadur, Ravi Sharma, Mridula |
| author_sort | Lokireddy, Sudarsanareddy |
| collection | NTU |
| description | Humoral and tumoral factors collectively promote cancer-induced
skeletal muscle wasting by increasing protein degradation.
Although several humoral proteins, namely TNFα (tumour
necrosis factor α) and IL (interleukin)-6, have been shown to
induce skeletal muscle wasting, there is a lack of information
regarding the tumoral factors that contribute to the atrophy of
muscle during cancer cachexia. Therefore, in the present study,
we have characterized the secretome of C26 colon cancer cells to
identify the tumoral factors involved in cancer-induced skeletal
muscle wasting. In the present study, we show that myostatin, a
procachectic TGFβ (transforming growth factor β) superfamily
member, is abundantly secreted by C26 cells. Consistent with
myostatin signalling during cachexia, treating differentiated
C2C12 myotubes with C26 CM (conditioned medium) resulted
in myotubular atrophy due to the up-regulation of musclespecific
E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger
protein 1), and enhanced activity of the ubiquitin–proteasome
pathway. Furthermore, the C26 CM also activated ActRIIB
(activin receptor type II B)/Smad and NF-κB (nuclear factor
κB) signalling, and reduced the activity of the IGF-I (insulin-like
growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway,
three salient molecular features of myostatin action in skeletal
muscles. Antagonists to myostatin prevented C26 CM-induced
wasting in muscle cell cultures, further confirming that tumoral
myostatin may be a key contributor in the pathogenesis of cancer
cachexia. Finally, we show that treatment with C26 CM induced
the autophagy–lysosome pathway and reduced the number of
mitochondria in myotubes. These two previously unreported
observations were recapitulated in skeletalmuscles collected from
C26 tumour-bearing mice. |
| first_indexed | 2024-10-01T02:48:03Z |
| format | Journal Article |
| id | ntu-10356/98861 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:48:03Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/988612022-02-16T16:31:03Z [Retracted] Myostatin is a novel tumoral factor that induces cancer cachexia Lokireddy, Sudarsanareddy Wijesoma, Isuru Wijerupage Bonala, Sabeera Wei, Meng Sze, Siu Kwan McFarlane, Craig Kambadur, Ravi Sharma, Mridula School of Biological Sciences DRNTU::Science::Biological sciences Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGFβ (transforming growth factor β) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of musclespecific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin–proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type II B)/Smad and NF-κB (nuclear factor κB) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy–lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletalmuscles collected from C26 tumour-bearing mice. 2013-07-31T09:17:24Z 2019-12-06T20:00:34Z 2013-07-31T09:17:24Z 2019-12-06T20:00:34Z 2012 2012 Journal Article Lokireddy, S., Wijesoma, I., Bonala, S., Wei, M., Sze, S., McFarlane, C., Kambadur, R.,& Sharma, M. (2012). Myostatin is a novel tumoral factor that induces cancer cachexia. Biochemical Journal, 446(1), 23-36. [Retracted] https://hdl.handle.net/10356/98861 http://hdl.handle.net/10220/12677 10.1042/BJ20112024 22621320 en Biochemical journal |
| spellingShingle | DRNTU::Science::Biological sciences Lokireddy, Sudarsanareddy Wijesoma, Isuru Wijerupage Bonala, Sabeera Wei, Meng Sze, Siu Kwan McFarlane, Craig Kambadur, Ravi Sharma, Mridula [Retracted] Myostatin is a novel tumoral factor that induces cancer cachexia |
| title | [Retracted]
Myostatin is a novel tumoral factor that induces cancer cachexia |
| title_full | [Retracted]
Myostatin is a novel tumoral factor that induces cancer cachexia |
| title_fullStr | [Retracted]
Myostatin is a novel tumoral factor that induces cancer cachexia |
| title_full_unstemmed | [Retracted]
Myostatin is a novel tumoral factor that induces cancer cachexia |
| title_short | [Retracted]
Myostatin is a novel tumoral factor that induces cancer cachexia |
| title_sort | retracted myostatin is a novel tumoral factor that induces cancer cachexia |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/98861 http://hdl.handle.net/10220/12677 |
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