Cancer molecule mystery solved

Cancer Research UK

Cancer Research UK scientists have uncovered a major clue towards solving the enduring mystery of how one of the most important known cancer molecules helps cause the disease.

Writing in this week's edition of the journal Nature, they report precise details of how the molecule called Myc cranks up the rate of growth of dividing cancer cells by sending one of the cell's key factories into overdrive.

Myc becomes overactive in many types of cancer and contributes to one in seven of all cancer deaths, but until now, scientists had been puzzled by how the molecule worked. The new discovery may help in the design of anti-cancer drugs to block the action of Myc and prevent cancer cells from dividing.

A cell has to grow to a certain size before it can divide in two, which it achieves by making a wide variety of protein molecules.

Because cancer cells divide so much more often than their healthy counterparts, they have to make proteins much more quickly than usual. Scientists suspected that Myc was crucial for speeding up the rate of protein production but how it managed it was a mystery.

Cancer Research UK scientists from the University of Glasgow in collaboration with colleagues from the Fred Hutchinson Research Center in Seattle - investigated the effect of the molecule on a crucial component of a cell's growth machinery - called RNA polymerase III. This is one of the cell's factories, churning out many of the molecules that allow a cell to grow and divide.

Researcher Nati Gomez, working under team leader Professor Bob White, found that Myc increased the work-rate of RNA polymerase III by about 12 times, allowing it to make sufficient raw materials to fuel cancer's rapid cell division.

Professor White, of the Institute of Biomedical and Life Sciences, University of Glasgow, says: "In the words of one of my colleagues, we have a mountain of evidence for the importance of Myc, but our knowledge of its function has amounted to little more than a molehill. But our new study helps provide a clear indication of how the molecule works."

Myc seems to latch on to RNA polymerase III via an intermediary molecule called TFIIIB, providing the impetus to put the cellular factory into overdrive. Scientists also know that Myc can affect a second factory molecule RNA polymerase II giving it an unprecedented ability to control the rate of cell growth.

Interfering with some of the functions of Myc perhaps by preventing it from interacting with RNA polymerase III could hamper the molecule¹s ability to speed up growth and might prevent cancer cells from dividing.

Prof White adds: "Myc seems to behave like the central manager of a number of different factories, with the ability to send production lines into overdrive when the need arises. If we can somehow prevent it from sending out its instructions, that could be a key way of keeping the growth of cancer cells in check."

Sir Paul Nurse, Chief Executive of Cancer Research UK, says: "Cancer cells are cells at full throttle, with every part of their molecular machinery working hard to fuel their excessively rapid growth and division.

"We've long suspected that Myc was one of the key molecules responsible for driving cell growth, but we¹ve lacked evidence about how the molecule worked, and that's left us powerless to develop therapies to intervene.

"This new study is extremely important. It fills a big hole in our understanding of cancer on the molecular level and gives us a promising new angle of attack for future treatments."

ENDS