NDLI: Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway

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Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway

Content Provider	Scilit
Author	Li, Zhiqiang Razavi, Pedram Li, Qing Toy, Weiyi Liu, Bo Ping, Christina Hsieh, Wilson Sanchez-Vega, Francisco Brown, David N. Paula, Arnaud F. Da Cruz Morris, Luc Selenica, Pier Eichenberger, Emily Shen, Ronglai Schultz, Nikolaus Rosen, Neal Scaltriti, Maurizio Brogi, Edi Baselga, Jose Reis-Filho, Jorge S. Chandarlapaty, Sarat
Copyright Year	2018
Description	Journal: Cancer Cell Summary Cyclin dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) are effective in breast cancer; however, drug resistance is frequently encountered and poorly understood. We conducted a genomic analysis of 348 estrogen receptor-positive $(ER^{+}$) breast cancers treated with CDK4/6i and identified loss-of-function mutations affecting FAT1 and RB1 linked to drug resistance. FAT1 loss led to marked elevations in CDK6, the suppression of which restored sensitivity to CDK4/6i. The induction of CDK6 was mediated by the Hippo pathway with accumulation of YAP and TAZ transcription factors on the CDK6 promoter. Genomic alterations in other Hippo pathway components were also found to promote CDK4/6i resistance. These findings uncover a tumor suppressor function of Hippo signaling in $ER^{+}$ breast cancer and establish FAT1 loss as a mechanism of resistance to CDK4/6i.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294301/pdf http://www.cell.com/article/S1535610818305270/pdf
ISSN	15356108
e-ISSN	18783686
DOI	10.1016/j.ccell.2018.11.006
Journal	Cancer Cell
Issue Number	6
Volume Number	34
Language	English
Publisher	Elsevier BV
Publisher Date	2018-12-01
Access Restriction	Open
Subject Keyword	Journal: Cancer Cell Cell Biology Cdk4/6 Inhibitors Hippo Pathway Breast Cancer Drug Resistance
Content Type	Text
Resource Type	Article
Subject	Cell Biology Cancer Research Oncology

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