Researchers uncover another potential Achilles' heel for breast cancer cells
Our scientists have discovered a new mechanism that helps breast cancer cells adapt to cope with the pressures of rapid growth. This research reveals a promising new target for future cancer treatments.
Scientists at the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research London, found a previously unknown way that breast cancer cells manage stress inside the cell.
The team found that breast cancer cells become highly dependent on a protein called GPR89. By moving this protein to a different part of the cell, they can cope better with conditions that might otherwise damage or kill them.
These findings, published in Nature Communications, suggest that blocking GPR89 could offer a highly selective way to kill tumour cells while sparing healthy tissue. And, they could also have implications for other types of cancer driven by similar biological processes.
Under pressure
Changes to certain genes can drive cells to grow and divide uncontrollably. These altered genes, called oncogenes, help fuel cancer growth. But they also create stress inside the cells.
One place this stress builds up is the endoplasmic reticulum, or ER. This is a structure inside cells that makes and processes proteins.
When certain cancer associated genes push cells to grow rapidly, the ER can become overloaded. And if this pressure becomes too great, it can damage the cells or cause them to die.
The researchers wanted to understand how breast cancer cells cope with this challenge.
A hidden support system
The team discovered that breast cancer cells redirect GPR89, a protein previously known for controlling acidity levels in another cell compartment, to the ER.
In its new location, it helps regulate the chemical conditions inside the ER, allowing cancer cells to cope better with the stress of rapid growth.
This means cancer cells can benefit from the genes driving their growth while limiting the damage those same genes cause.
The discovery also reveals another way that cancer associated genes can work together. Alongside genes that encourage growth, cancer cells can rely on support systems that help them withstand the resulting pressure.
Crucially, the experiments showed that breast cancer cells become particularly reliant on GPR89 when it is working in the endoplasmic reticulum. This creates a weakness, because cancer cells may need the protein much more than healthy cells do.
Finding new treatments
One of the longstanding challenges in cancer treatment is identifying weaknesses that are unique to tumour cells. Many existing therapies also affect healthy tissue, leading to unwanted side effects.
The researchers believe that blocking GPR89 could offer a way to target breast cancer cells while leaving healthy cells relatively unaffected.
This is early research. Substantial further work is needed before an approach targeting GPR89 could benefit people with breast cancer. But this discovery gives scientists a strong reason to explore whether treatments could exploit this weakness.
This work reveals an entirely new way in which cancer cells can gain the benefits of oncogene activation while controlling the harmful stress that those same oncogenes create. What is particularly exciting is that this adaptation appears to create a cancer-specific dependency on GPR89, opening up the possibility of developing highly selective therapies that target tumour cells.
Looking ahead
The findings could also have implications beyond breast cancer. Many other cancers are driven by oncogenes and experience high levels of stress in the ER.
If these cancers depend on similar ways of managing that stress, targeting GPR89 or related processes could offer opportunities for treatment.
While further work is needed, our discovery establishes an important new concept in cancer biology and could ultimately lead to treatments that exploit a weakness shared by a much broader range of cancers than breast cancer alone.
Want to know more?
By understanding how breast cancer cells adapt to survive, our scientists are uncovering weaknesses that could help shape the treatments of the future.