Flipping the switch in cancer

Effective treatment for certain cancers
This discovery by Dr Polly Leilei Chen (right), Dr Song Yangyang (left) and their team could lead to more effective treatment of certain cancers.

The seemingly impenetrable façade of cancer hides multiple weaknesses. Hunting for such weaknesses, Dr Polly Leilei Chen from the Cancer Science Institute of Singapore and her team found that the internal signaling system can be manipulated to slam the brakes on uncontrolled cell growth in liver cancer, and possibly other cancers.

Chen, who also holds an appointment at the Yong Loo Lin School of Medicine, and her team discovered this brake while studying a key cancer gene called coatomer subunit α” (COPA) that influences the development of not just liver cancer, but also throat (or oseophagus), stomach and breast cancers.


Conveying a different message

When cells multiply, the information carried in genes or DNA, is first transcribed into a “message” (or RNA). “Letters” known as nucleotides form this message, which is then decoded to assemble the proteins needed within a specific cell.

During RNA editing however, some of the nucleotides along the RNA are changed. This changes certain words, which causes a different message to be received when it is decoded.

Depending on where the changes occur, they may affect how proteins are assembled in the cell, resulting in a different version that is formed.


Maintaining a delicate balance

By studying the RNA that is transcribed from the COPA gene in clinical samples of cancerous liver tissues, the researchers found that each cell contained both edited and unedited versions of COPA that were present in varying amounts.

Cells were more likely to turn cancerous when COPA was largely unedited (“wild type” COPA). When more edited copies of COPA were present, however, a cellular mechanism that promotes cancer through triggering uncontrolled cell growth is suppressed.

“With this new knowledge, we can now look into how RNA editing contributes to cancer by altering their protein sequences and how we can restore cancer-suppressing processes mediated by RNA editing in the cell,” said Chen.

Her team is now trying to find a way to boost the natural RNA editing mechanisms in cancerous cells to tip the balance in favour of the edited version of COPA as a potential treatment option for cancer.

Adapted from NUS News.