Though microRNA’s have been known of playing a role in cancer development for some time, an MIT postdoc demonstrated that they play a significant role in the metastatic process of cancer cells.
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, or spread.
Now, working in the lab of MIT Biology Professor and 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…
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.
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.
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Image caption: Small secondary tumors (shown in green) formed in the lungs of mice after Li Ma, a postdoctoral researcher at the Whitehead Institue for Biomedical Research, inserted human breast cancer cells into their mammary fat pads. The cancer cells, which normally don’t metastasize, acquired the ability to move and invade when Ma boosted the level of a single microRNA.