Breast cancer accomplice discovered
August 24, 2015
In the current studies, funded by a grant from the National Cancer Institute, Kumar's team finds that MTA1 expression triggers cancer-causing signals from Wnt1 in human breast cancer cells. This Wnt1 signaling cascade leads to tumors, they demonstrate, by showing that 8.8 percent of mice bearing artificially elevated levels of MTA1s grew tumors in their mammary glands.
To get down to the details, Kumar and his fellow researchers show that MTA1 and MTA1s activate the cancer-causing pathway by reducing the levels of a protein known as Six3. This protein is known to inhibit Wnt1 in brain cells, but in their study involving breast cancer cells, it inhibited Wnt1 in a rather non-intuitive way. Six3 normally puts the brakes on Wnt signaling, and so when MTA1 obstructed Six3, Wnt1 signals let loose. In addition, the team found that MTA1s also promoted Wnt signaling directly and through another known Wnt-related pathway - namely ERK-mediated GSK3??.
Because inflammation may drive MTA1, and since inflammation is believed to drive certain forms of cancer, Kumar's work suggests one possible reason for why worsening cancer progression has been correlated with other inflammation-inducers. "We've raised the next level question," says Kumar, "and now we're going back into the lab to ask if this pathway plays a role in inflammation-related cancer."
SOURCE The George Washington University School of Medicine and Health Sciences