MicroRNA convicted of triggering metastasis

Sep 26, 2007

The jury is in: microRNAs can cause tumors to metastasize. These tiny molecules fine-tune protein production and play a powerful role in biological processes ranging from development to aging. Now scientists have proved that they can prompt otherwise sedentary cancer cells to move and invade other tissues.

Labs have been probing the relationship between aberrant microRNA levels and cancer for several years. They’ve shown that some microRNAs cause normal cells to divide rapidly and form tumors, but they’ve never demonstrated that microRNAs subsequently cause cancer cells to metastasize.

Now, working in the lab of Whitehead Member Robert Weinberg, postdoctoral fellow Li Ma has coaxed cancer cells to break away from a tumor and colonize distant tissues in mice by simply increasing the level of one microRNA. Her results appear online in Nature on September 26.

“Li has shown that a specific microRNA is able to cause profound changes in the behavior of cancer cells, which is striking considering that 10 years ago no one suspected microRNAs were involved in any biological process,” says Weinberg, who is also an MIT professor of biology.

Ma began with a list of 29 microRNAs expressed at different levels in tumors versus normal tissue. She examined their production in two groups of cancer cells—metastatic and non-metastatic. Metastatic cancer cells (including those taken directly from patients) contained much higher levels of one microRNA called microRNA-10b.

Next, Ma forced non-metastatic human breast cancer cells to produce lots of microRNA-10b by inserting extra copies of the gene. She injected the altered cancer cells into the mammary fat pads of mice, which soon developed breast tumors that metastasized.

So what caused this stunning metamorphosis?

MicroRNAs typically disrupt protein production by binding to the messenger RNAs that copy DNA instructions for proteins and carry them to “translators.” Ma used a program developed in the lab of Whitehead Member David Bartel to search for the target of microRNA-10b. She identified several candidates, including the messenger RNA for a gene called HoxD10.

Generally involved in development, Hox proteins control many genes active in an embryo. Some Hox proteins have also been implicated in cancer. HoxD10, for example, can block the expression of genes required for cancer cells to move—essentially applying the brakes to a migration process.

To test whether she had removed the brakes during her experiment, awakening the dormant migration process, Ma boosted the level of HoxD10 in the cancer cells with artificially high levels of microRNA-10b. The cells lost their newly acquired abilities to move and invade.

“I was able to fully reverse microRNA-10b induced migration and invasion, suggesting that HoxD10 is indeed a functional target,” Ma explains.

“During normal development, this microRNA probably enables cells to move from one part of the embryo to another,” adds Weinberg. “Its original function has been co-opted by carcinoma cells.”

Source: Whitehead Institute for Biomedical Research

Explore further: Novel marker discovered for stem cells derived from human umbilical cord blood

add to favorites email to friend print save as pdf

Related Stories

Ultrasensitive particles offer new way to find cancer

Aug 31, 2011

About 10 years ago, scientists discovered a new type of genetic material called microRNA, which appears to turn genes on or off inside a cell. More recently, they found that these genetic snippets often go ...

Recommended for you

New pain relief targets discovered

6 hours ago

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

Building 'smart' cell-based therapies

7 hours ago

A Northwestern University synthetic biology team has created a new technology for modifying human cells to create programmable therapeutics that could travel the body and selectively target cancer and other ...

Proper stem cell function requires hydrogen sulfide

10 hours ago

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry ...

User comments : 0

More news stories

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...