Good news! Cancer is history (soon)!
"Key points
- Having too many or too few chromosomes is fatal to normal cells.
- But many cancer cells often have the incorrect number of chromosomes.
- A new study finds cancer cells can tolerate missing chromosomes by boosting the production of proteins the chromosome is responsible for.
- The findings could inform new targets for cancer therapies.
...
A hallmark of cancerous cells is an abnormal number of chromosomes or chromosome arms, known as aneuploidy. While aneuploidy is detrimental to regular cells, it occurs in as many as 90% of tumors. How cancer cells tolerate this chromosomal imbalance has remained unclear.
To better understand how these cells function ... uses mass spectrometry to measure the amounts of proteins in cells, as well as how they're produced and removed. Through this technique, Liu’s team previously discovered that cells with too many chromosomes degraded excess proteins at higher rates. The findings supported the predominant view in biology research that cells maintain the correct balance of proteins primarily by adjusting the rate at which they break proteins down. ...
To their surprise, they found that protein degradation rates overall remained the same as normal cells. Rather, cells selectively increased synthesis rates of the proteins encoded by the missing chromosome, challenging current conceptions. ..."
From the highlights and abstract:
"Highlights
• Proteostasis mechanisms in gain- and loss-type single-arm aneuploidy are distinct
• The lost-type aneuploidy displays no change in global and relative protein degradation
• Chromosome loss is compensated by relative upregulation of protein synthesis in complexes
• Proteins in complexes encoded on the lost chromosome show increased thermal stability
Summary
How aneuploid cells tolerate chromosome arm gains or losses remains an open question. Using an isogenic human lung cell model with either chromosome 3p loss or 3q gain, combined with quantitative mass spectrometry and isotopic labeling, we reveal distinct proteostasis mechanisms for gain- and loss-type aneuploidy.
Surprisingly, while compensation for 3q gain is primarily driven by increased degradation of excess protein complex subunits, 3p loss is neither counteracted by global protein degradation nor selectively reduced degradation.
Rather, there is a relative upregulation in protein synthesis of those 3p-encoded proteins that participate in stable protein complexes to maintain functional complex stoichiometry. Additionally, 3p-encoded proteins that are in a complex show increased thermal stability in loss-type aneuploidy, potentially via their interactions with other proteins from euploid chromosomes. Together, our findings uncover distinct proteomic buffering strategies that enable cells to tolerate either excessive or deficient single-arm aneuploidy."
"Aneuploidy, defined as the abnormal gain or loss of chromosomes or chromosome arms, is a hallmark of human genetic syndromes and many cancers.
While somatic aneuploidy is rare in healthy human tissues it is highly prevalent in cancer, with 90% of solid tumors exhibiting aneuploidy. This contributes to tumor evolution, metastasis, and drug resistance. In lung squamous cell carcinoma (LSCC), for example, chromosome (chr) 3q is gained in over 60% of tumors, whereas chr3p is lost in 78%. ..."
Graphical abstract
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