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Chromosomal instability is a feature of solid tumors (such as cancer)
.
Similarly, cellular senescence is a process that is highly related to cellular senescence, and its connection with cancer is becoming more and more obvious
"Chromosomal instability and senescence are two characteristics shared by most tumors, but the relationship between the two is unclear
.
Our research shows that senescence may be one of the intermediate links between chromosomal changes and cancer," Dr.
Dr.
Jerry Joy, the first author of this article published in the journal Developmental Cell, said: "The behavior we see in chromosomal unstable cells makes us think that they may be senescent cells, and that is indeed the case! "
This study was conducted on Drosophila, a commonly used animal model in biomedicine.
The described mechanism may help understand the contribution of chromosomal instability and aging to cancer, and help identify possible treatments.
Target
.
Reversing the effects of chromosomal instability
Researchers from the Development and Growth Control Laboratory have proven that in epithelial tissues with highly unstable chromosomes, those cells with altered chromosome number balance separate from neighboring cells and enter senescence
.
The characteristic of senescent cells is that the cell cycle is permanently stopped and large amounts of protein are secreted
If senescent cells are not immediately eliminated by the body, they will promote the abnormal growth of surrounding tissues, leading to malignant tumors
.
Dr.
Milan said: "If we can identify the mechanism that reduces the number of senescent cells, then we can reduce the growth of these tumors
Cells with an unbalanced number of chromosomes will accumulate a large number of abnormal mitochondria, which will produce high levels of oxidative stress, which in turn activates the JNK signaling pathway and triggers aging
.
"We have shown that reducing this high abnormal number of mitochondria, or regulating the oxidative stress caused by them, is sufficient to reduce the number of senescent cells and the negative effects of chromosomal instability," Dr.
These findings have opened up new research approaches for finding therapeutic targets and reducing the level of senescence caused by chromosomal instability in solid tumors
.
From flies to mammals
Vinegar fly (Drosophila melanogaster) has a wide range of applications in the field of biomedicine
.
In cancer research, it is a valuable animal model because it has a short life cycle and a large number of genetic tools are available.
There are the same genes as humans, but the degree of redundancy is low
In fact, experiments designed to analyze the causal relationship between cell behaviors or characteristics in human tumors, such as chromosomal instability and aging, are easier to analyze in this model organism
.
Future laboratory work will continue to analyze the molecular mechanism of cell behavior in solid tumors of epithelial origin induced by pure chromosomal instability
.
Dr.
Original search:
Proteostasis failure and mitochondrial dysfunction leads to aneuploidy-induced senescence
Jery Joy, Lara Barrio, Celia Santos-Tapia, Daniela Rom?o, Nikolaos Nikiforos Giakoumakis, Marta Clemente-Ruiz & Marco Milán
Developmental Cell (2021) DOI: 10.
1016/j.
devcel .
