A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components

Monique B. Nilsson; Huiying Sun; Jacqulyne Robichaux; Matthias Pfeifer; Ultan McDermott; Jon Travers; Lixia Diao; Yuanxin Xi; Pan Tong; Li Shen; Mia Hofstad; Masanori Kawakami; Xiuning Le; Xi Liu; You-Hong Fan; Alissa Poteete; Limei Hu; Marcelo V. Negrão; Hai T. Tran; Ethan Dmitrovsky; David H. Peng; Don L. Gibbons; Jing Wang; John V. Heymach

doi:10.1126/scitranslmed.aaz4589

A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components

Monique B. Nilsson(The University of Texas MD Anderson Cancer Center), Huiying Sun(The University of Texas MD Anderson Cancer Center), Jacqulyne Robichaux(The University of Texas MD Anderson Cancer Center), Matthias Pfeifer(AstraZeneca (United Kingdom)), Ultan McDermott(AstraZeneca (United Kingdom)), Jon Travers(AstraZeneca (United Kingdom)), Lixia Diao(The University of Texas MD Anderson Cancer Center), Yuanxin Xi(The University of Texas MD Anderson Cancer Center), Pan Tong(The University of Texas MD Anderson Cancer Center), Li Shen(The University of Texas MD Anderson Cancer Center), Mia Hofstad(The University of Texas MD Anderson Cancer Center), Masanori Kawakami(The University of Texas MD Anderson Cancer Center), Xiuning Le(The University of Texas MD Anderson Cancer Center), Xi Liu(The University of Texas MD Anderson Cancer Center), You-Hong Fan(The University of Texas MD Anderson Cancer Center), Alissa Poteete(The University of Texas MD Anderson Cancer Center), Limei Hu(The University of Texas MD Anderson Cancer Center), Marcelo V. Negrão(The University of Texas MD Anderson Cancer Center), Hai T. Tran(The University of Texas MD Anderson Cancer Center), Ethan Dmitrovsky(The University of Texas MD Anderson Cancer Center), David H. Peng(The University of Texas MD Anderson Cancer Center), Don L. Gibbons(The University of Texas MD Anderson Cancer Center), Jing Wang(The University of Texas MD Anderson Cancer Center), John V. Heymach(The University of Texas MD Anderson Cancer Center)

Science Translational Medicine

September 2, 2020

10.1126/scitranslmed.aaz4589

Cited by 178Open Access

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Abstract

expression correlated with expression of genes encoding SAC proteins and was associated with a worse clinical outcome. These data revealed the YAP/FOXM1 axis as a central regulator of EMT-associated EGFR TKI resistance and that this pathway, along with SAC components, are therapeutic vulnerabilities for targeting this multidrug-resistant phenotype.

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