Functions of Mob1A/1B in development and oncogenesis

Hippo通路在进化上是保守的，并且脊椎动物Hippo通路已经涉及调节细胞接触抑制、器官大小和肿瘤发生。Mob 1A/1B是Lats激酶家族的结合伴侣和强共激活因子，也是Hippo信号通路的成员，但Mob 1A/1B蛋白在体内的正常功能尚不清楚，为了明确Mob 1A/1B的功能，我们制备了Mob 1A和Mob 1B缺失突变小鼠。我们发现Mob 1A/1 B双纯合突变小鼠在原肠胚形成时死亡，因此Mob 1A/B是小鼠胚胎发生所必需的。部分突变体产生了多种肿瘤。此外，一半的人毛根癌样本显示Mob 1A/1B失活和雅普激活。这些观察结果表明，Hippo信号分子的丢失可能是癌症进展的重要驱动因素。

The Hippo pathway is evolutionarily conserved, and the vertebrate Hippo pathway has been implicated in regulating cell contact inhibition, organ size, and tumorigenesis. The Mob1A/1B are the binding partners and strong co-activators of Lats kinases family, and the members of the Hippo pathway.However, the normal functions of Mob1A/1B proteins in vivo had been unknown.To define the functions of mammarian Mob1A/1B, we generated Mob1A and 1B null mutant mice. We showed Mob1A/1B double homozygous mutant mice died at gastrulation.Thus, Mob1A/B is essential for murine embryogenesis. Partially mutants developed a variety of tumors. Moreover, half of human trichilemmal carcinoma samples showed Mob1A/1B inactivation and YAP activation.These observations suggest that the loss of Hippo signaling molecules can be an important driver of cancer progression.