Turn out the light: 'Switch' determines cancer cell fate

May 3, 2013 by Anne Ju
Turn out the light: 'Switch' determines cancer cell fate
A graphical abstract illustrates how a microRNA acts as a hard switch to determine colon cancer stem cell fate. Credit: Xiling Shen

(Phys.org) —Like picking a career or a movie, cells have to make decisions – and cancer results from cells making wrong decisions.

At the , wrong decisions can be made right. Cornell engineers with clinicians at Weill Cornell Medical College have discovered that colon cancer stem cells, a particularly malignant population of cancer cells, are able to switch between the decision to proliferate or to remain constant – and this "switch" is controlled by a little-studied molecule called microRNA.

The research, published online May 2 in the journal Cell Stem Cell, was led by senior author Xiling Shen, assistant professor of electrical and computer engineering, with clinician Steven M. Lipkin, associate professor of medicine at Weill Cornell Medical College. The multidisciplinary work involves engineers, biologists and doctors.

Cancer stem cells live in tumors and share characteristics of regular stem cells – they "decide" what to become. In early stage, noninvasive tumors, say the researchers, cancer stem cells are biased toward asymmetric division – meaning the population of cancer stem cells remains constant. But in more malignant, late-stage tumors, these cells tend to promote symmetric division, or fast proliferation, by making identical copies of themselves, which leads to invasion and metastasis, or spread of .

MicroRNA, known as a non-coding RNA, is a relatively understudied molecule because unlike regular , it doesn't make proteins, and therefore, its importance in has not been well characterized.

"MicroRNA, which is usually thought to be dispensable in normal tissue, has been largely overlooked in its role in determining cancer outcomes," Shen said.

Using clinically relevant samples from colon cancer patients at NewYork-Presbyterian/Weill Cornell Medical Center who provided permission, the team conducted experiments to determine a link between the presence of a microRNA called miR-34a and tumor size, metastatic potential and chemoresistance in cancer patients.

They discovered that microRNA acts as a sharp on-off switch that controls the mode of division of colon cancer stem cells, symmetric or asymmetric, in a mechanism distinct from protein regulators.

By changing the number of binding sites of microRNA in a given sample, the dynamics of the system can be tuned to be sharp or gradual – lots of microRNA binding sites make the switch very sharp; fewer make the switch more gradual.

By studying how microRNA affects cancer in real patient tumors, the researchers hypothesize that late-stage tumors try to shut down the switching mechanism so that cells are free to produce even more cancer stem cells. This is why therapies that might arise from this discovery would need to be "upstream" of the microRNA binding – that is, it's better to control the switching at the microRNA level rather than just increasing the population of microRNA later, when the cancer has already spread.

Shen, a trained electrical engineer, confesses a longtime fascination with the concept of how cells make decisions – the classical example being stem cells, which must decide whether and when to differentiate into myriad other types of cells and how to spatially allocate them. But what controls this process? Shen likes to think of cells as circuits – how they are wired determines not only their decision-making prowess, but also how robust those decisions are.

The study is titled "A MicroRNA miR-34a Regulated Bimodal Switch Targets Notch in ."

Explore further: Common cancer gene sends death order to tiny killer

More information: www.cell.com/cell-stem-cell/abstract/S1934-5909%2813%2900097-0

Related Stories

Common cancer gene sends death order to tiny killer

May 31, 2007

Scientists at Johns Hopkins have discovered one way the p53 gene does what it's known for—stopping the colon cancer cells. Their report will be published in the June 8 issue of Molecular Cell.

MicroRNA suppresses prostate cancer stem cells and metastasis

January 16, 2011

A small slice of RNA inhibits prostate cancer metastasis by suppressing a surface protein commonly found on prostate cancer stem cells. A research team led by scientists at The University of Texas MD Anderson Cancer Center ...

Recommended for you

Scientists discover key clues in turtle evolution

September 2, 2015

A research team led by NYIT scientist Gaberiel Bever has determined that a 260-million year-old fossil species found in South Africa's Karoo Basin provides a long awaited glimpse into the murky origins of turtles.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.