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Merlin protein found to control liver stem cells, prevent tumor development
Date:8/12/2010

ceptors. One of these is the epidermal growth factor receptor (EGFR), and oversignaling by that protein is known to lead to several types of cancer. The current study was designed to investigate the role of NF2 and merlin in the fetal and adult mouse liver, including possible involvement with tumor development.

The researchers found that infant mice lacking functioning NF2 in their livers developed dramatic overgrowth of liver stem cells, to the point of crowding out hepatocytes. Mice that did not die from a lack of functioning liver cells soon developed the two major types of liver cancer, and the fact that stem cell overgrowth preceded tumor development strongly suggested that the undifferentiated progenitors were the source of the tumors. Blocking the expression of NF2 in the livers of adult mice had minimal effect on the animals unless a portion of the liver was surgically removed, setting off the regeneration process and leading to the same stem cell overproliferation and tumor development.

McClatchey explains that the study's findings provide new information about liver stem cells and how their proliferation is controlled; identifies a new animal model for liver cancer, the lack of which has seriously impeded understanding the disease; and suggests that liver tumors may originate from liver stem cells and that excess EGFR signaling leads to liver tumor development. "These results are consistent with our previous studies showing that merlin helps to regulate EGFR activity at the cell membrance," she says. "We also showed that merlin's role in cell-to-cell communication is essential for cells to stop growing when they fill the appropriate space. Since liver progenitors need to be poised to regenerate in case of injury, they may be particularly sensitive to the loss of merlin's regulatory function." McClatchey is an associate professor of Pathology at Harvard Medical School.


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Contact: Katie Marquedant
kmarquedant@partners.org
617-726-0337
Massachusetts General Hospital
Source:Eurekalert

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