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.