A scientist reports proving the ability of miRNAs to prompt otherwise sedentary cancer cells to move and invade other tissues. She found that high levels of miRNA-10b are associated with breast cancer metastasis in mice.
Previous research has shown that some miRNAs cause normal cells to divide rapidly and form tumors. Until now, however, it had not been demonstrated that miRNAs subsequently cause cancer cells to metastasize.
Working in Robert Weinberg’s lab at the Whitehead Institute for Biomedical Research, postdoctoral fellow Li Ma was able to coax cancer cells to break away from a tumor and colonize distant tissues in mice by increasing the level of one miRNA.
Ma began with 29 miRNAs that have shown differential expression in tumors versus normal tissue. She examined their production in metastatic and nonmetastatic cancer cells. Ma found that the metastatic cells including those taken directly from patients contained much higher levels of miRNA-10b.
Next, Ma forced nonmetastatic human breast cancer cells to produce alot of miRNA-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.
To find out what caused this change, Ma searched for the target of microRNA-10b. She identified several candidates including the messenger RNA for a gene called HoxD10. Some Hox proteins have already been implicated in cancer, Ma points out. HoxD10, for example, can block the expression of genes required for cancer cells to move.
To test whether she removed these brakes during her experiment, Ma boosted the level of HoxD10 in the cancer cells with artificially high levels of miRNA-10b. The cells lost their newly acquired abilities to move and invade. “I was able to fully reverse miRNA-10b induced migration and invasion, suggesting that HoxD10 is indeed a functional target.”
Weinberg, who is also an MIT professor of biology, hypothesizes that, “During normal development, this miRNA probably enables cells to move from one part of the embryo to another. Its original function has been co-opted by carcinoma cells.”
Ma reports that the results of this research appear online in Nature on September 26.