The role of Motin family proteins in tumorigenesis-an update

The Motin protein family consists of three members: AMOT (p80 and p130 isoforms), AMOT-like protein 1 (AMOTL1), and AMOT-like protein 2 (AMOTL2). The family members play an important role in processes such as cell proliferation, migration, angiogenesis, tight junction formation, and cell polarity. These functions are mediated through the involvement of the Motins in the regulation of different signal transduction pathways, including those regulated by small G-proteins and the Hippo-YAP pathway. One of the more characterized aspects of Motin family function is their role in regulating signaling through the Hippo-YAP pathway, and while some studies suggest a YAP-inhibitory function other studies indicate the Motins are required for YAP activity. This duality is also reflected in previous reports, often contradictory, that suggest the Motin proteins can function as oncogenes or tumor suppressors in tumorigenesis. In this review we summarize recent findings and integrate that with the existing work describing the multifunctional role of the Motins in different cancers. The emerging picture suggests that the Motin protein function is cell-type and context dependent and that further investigation in relevant cell types and whole organism models is required for the elucidation of the function of this protein family.