Data from CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC Article Swipe

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Jeffrey H. Becker , Yandi Gao , Margaret Soucheray , Inés Pulido , Eiki Kikuchi , María Luisa Rodríguez , Rutu Gandhi , Aránzazu Lafuente-Sanchis , Miguel Aupí , Javier Alcácer Fernández-Coronado , Paloma Martín-Martorell , Antonio Cremades , José M. Galbis , Javier Alcácer , Camilla L. Christensen , Patricia Simms , Ashley Hess , Hajime Asahina , Michael Kahle , Fátima Al‐Shahrour , Jeffrey A. Borgia , Agustín Lahoz , Amelia Insa , Óscar Juan , Pasi A. Jänne , Kwok‐Kin Wong , Julián Carretero , Takeshi Shimamura ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/0008-5472.c.6510909

Although EGFR mutant–selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK–ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI–resistant persister cells. Many patients with non–small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutation, who progressed on EGFR inhibitors, demonstrated increased CXCR7 expression. These data suggest that CXCR7 inhibition could considerably delay and prevent the emergence of acquired EGFR TKI resistance in EGFR-mutant NSCLC.Significance:Increased expression of the chemokine receptor CXCR7 constitutes a mechanism of resistance to EGFR TKI in patients with non–small cell lung cancer through reactivation of ERK signaling.

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MAPK/ERK pathway Kinase Cancer research Medicine Chemistry Biochemistry

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/0008-5472.c.6510909
OA Status: gold
Related Works: 10
OpenAlex ID: https://openalex.org/W4392723284

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DOI: https://doi.org/10.1158/0008-5472.c.6510909

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Title: Data from CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC

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Type: preprint

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Language: en

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Publication year: 2023

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Publication date: 2023-03-31

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Authors: Jeffrey H. Becker, Yandi Gao, Margaret Soucheray, Inés Pulido, Eiki Kikuchi, María Luisa Rodríguez, Rutu Gandhi, Aránzazu Lafuente-Sanchis, Miguel Aupí, Javier Alcácer Fernández-Coronado, Paloma Martín-Martorell, Antonio Cremades, José M. Galbis, Javier Alcácer, Camilla L. Christensen, Patricia Simms, Ashley Hess, Hajime Asahina, Michael Kahle, Fátima Al‐Shahrour, Jeffrey A. Borgia, Agustín Lahoz, Amelia Insa, Óscar Juan, Pasi A. Jänne, Kwok‐Kin Wong, Julián Carretero, Takeshi Shimamura

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Landing page: https://doi.org/10.1158/0008-5472.c.6510909

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OA status: gold

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OA URL: https://doi.org/10.1158/0008-5472.c.6510909

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Concepts: MAPK/ERK pathway, Kinase, Cancer research, Medicine, Chemistry, Biochemistry

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Cited by: 0

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Related works (count): 10

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