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April 8, 2009

Mechanism of Cell-Type-Specific Signaling in Tumor Development Determined

  • Researchers from Mayo Clinic and Centre de Recherche en Cancérologie de Marseille have discovered the mechanisms behind two checkpoints in cell growth and development and tumor progession. They report that a protein called Erbin along with tumor suppressor Merlin control the activation of PAK2 in epithelial cells.

    PAK2 is a downstream component of TGF-ß signaling and a target for cancer growth and fibrotic tissue development. In epithelial cells, however, TGF-ß is unable to activate PAK2. “We decided to look at the factors that prevented PAK2 activation in epithelial cells,” explains Edward Leof, Ph.D., a Mayo Clinic biochemist who led the study, which appears in Developmental Cell. The paper is called “Erbin and the NF2 Tumor Suppressor Merlin Cooperatively Regulate Cell-Type-Specific Activation of PAK2 by TGF-ß.”

    The scientists found that Erbin controls Merlin, and when Merlin is absent or mutated, the result is schwannoma, a form of tumor involving Schwann cells, which make up the myelin sheath that covers nerves. Merlin has also reportedly been shown to play a part in causing melanoma, mesothelioma, and possibly colorectal cancers.

    Additionally, the researchers showed that in epithelial cells, which have high levels of Erbin, the formation of an Erbin/Merlin complex prevents PAK2 activity following growth factor stimulation. In the absence of Erbin or Merlin, however, TGF-ß stimulates PAK2 activity in some epithelia, overcoming a critical checkpoint in tumor progression.

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