NF2 Loss Promotes Oncogenic RAS-Induced Thyroid Cancers via YAP-Dependent Transactivation of RAS Proteins and Sensitizes Them to MEK Inhibition

NF2 缺失通过 YAP 依赖的 RAS 蛋白转录激活促进致癌 RAS 诱发的甲状腺癌,并使其对 MEK 抑制敏感

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作者:Maria E R Garcia-Rendueles, Julio C Ricarte-Filho, Brian R Untch, Iňigo Landa, Jeffrey A Knauf, Francesca Voza, Vicki E Smith, Ian Ganly, Barry S Taylor, Yogindra Persaud, Gisele Oler, Yuqiang Fang, Suresh C Jhanwar, Agnes Viale, Adriana Heguy, Kety H Huberman, Filippo Giancotti, Ronald Ghossein, Ja

Significance

Intensification of mutant RAS signaling through copy-number imbalances is commonly associated with transformation. We show that NF2/merlin inactivation augments mutant RAS signaling by promoting YAP/TEAD-driven transcription of oncogenic and wild-type RAS, resulting in greater MAPK output and increased sensitivity to MEK inhibitors.

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