Molecular Cell: Chromosome Errors Make Cancer More Resistant and Aggressive

Scientists have uncovered an important clue explaining why some tumors become especially resistant to treatment and spread more easily throughout the body.

The results of the new study were published in the journal Molecular Cell.

Researchers found that a key role may be played by an “incorrect” number of chromosomes in cancer cells.

Chromosomes are DNA structures that contain the instructions needed for a cell to function. Normally, during cell division, their number is strictly controlled: each new cell receives a complete and accurate set of genetic information.

But in tumors, this process is often disrupted — cells begin dividing too quickly, leading to errors: some cells gain extra chromosomes, while others lose them. This condition is known as aneuploidy.

For a long time, scientists believed these errors were simply a side effect of cancer. However, the new study published in Molecular Cell suggests that aneuploidy may actually help tumors survive.

The researchers discovered that cells with abnormal chromosome numbers contain 50–60% lower levels of the protein PARP1.

Under normal conditions, this protein acts as a kind of “self-destruction system”: it triggers cell death when a cell suffers severe DNA damage, such as damage caused by oxidative stress. This mechanism helps prevent damaged cells from multiplying.

But when PARP1 levels decrease, this protective system weakens. As a result, cancer cells are better able to survive damage that commonly occurs during treatment, such as chemotherapy or other stress-related exposures.

To test this, the researchers created laboratory models using aneuploid cells from intestinal, lung, and eye tissues. In every case, these abnormal cells survived better than normal cells, even when exposed to damaging conditions.

The team then investigated why PARP1 levels decline. They found that chromosome errors overload the cell’s “recycling stations” — lysosomes. This triggers a signaling chain involving the protein CEBPB, ultimately suppressing the production of PARP1.

In mouse experiments, reduced PARP1 levels made tumors more likely to spread to other organs. Conversely, increasing the amount of this protein reduced the ability of cancer cells to metastasize. Analysis of human tumors confirmed the same trend: metastatic cancers had lower PARP1 levels than primary tumors.

Scientists believe this discovery is important not only for understanding how cancer works, but also for future treatments. If researchers learn how to restore PARP1 levels or interfere with this stress pathway, it may become possible to slow tumor spread and improve the effectiveness of therapy.

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