Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Cancer subtype influences skeletal muscle defects. RAS pathway mutations, unlike PIK3CA, significantly impair muscle function and miR-486 levels, highlighting the need to consider cancer genomics for systemic therapies.
Area Of Science
- Oncology
- Molecular Biology
- Genetics
Background
- Cancer-induced skeletal muscle defects vary in severity.
- Genomic aberrations in cancer subtypes are implicated but poorly studied.
- Limited experimental data exists on cancer subtype-specific effects on skeletal muscle.
Purpose Of The Study
- To investigate how different breast cancer subtypes and oncogenic mutations affect skeletal muscle function.
- To correlate specific genomic aberrations with molecular changes in skeletal muscle.
- To identify potential biomarkers for cancer-induced muscle dysfunction.
Main Methods
- Utilized three distinct breast cancer patient-derived xenograft (PDX) models.
- Generated human breast epithelial cells transformed with HRASG12V or PIK3CAH1047R oncogenes.
- Assessed skeletal muscle function via rotarod performance and contraction force.
- Analyzed molecular markers in skeletal muscle and circulation (miR-486, Pax7, pAKT, p53, CXCL1, phospho-p38).
Main Results
- All PDX models showed impaired skeletal muscle function and reduced miR-486.
- Only the triple-negative breast cancer (TNBC) PDX activated phospho-p38 in muscle.
- HRASG12V-transformed cells, but not PIK3CA-transformed cells, caused significant skeletal muscle defects.
- HRASG12V tumors elevated circulating CXCL1 and altered muscle miR-486, Pax7, pAKT, and p53 levels.
Conclusions
- Mutant RAS-driven breast cancers distinctly impact skeletal muscle function compared to PIK3CA-driven cancers.
- Specific genomic aberrations, particularly in the RAS pathway, are critical determinants of cancer-induced systemic effects.
- Therapeutic strategies targeting cancer-induced skeletal muscle dysfunction should consider the underlying cancer genome.
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