NF2/Merlin Regulates Cell Proliferation and Cell Migration through YAP/TAZ and AMOT.

Abstract

The Hippo pathway is a central regulator of tissue homeostasis, organ growth, and tumorigenesis. NF2 (Neurofibromin 2, also known as Merlin) functions as a pivotal upstream component that integrates biochemical and mechanical cues to restrain the activity of the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), thereby limiting cell proliferation. In addition, NF2 regulates members of the Motin family proteins (AMOT, AMOTL1, and AMOTL2) through ubiquitin-mediated turnover to modulate YAP/TAZ signaling output. Moreover, NF2 controls AMOT proteolytic processing to reorganize the actin cytoskeleton, thereby influencing cell motility. Through these mechanisms, NF2 establishes a multilayered regulatory system that coordinates cell proliferation and cell migration. This review summarizes recent advances in how NF2 regulates YAP/TAZ and AMOT functions, focusing on their roles in tumor formation, metastasis, and angiogenesis.