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A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components
Open accessAbstract
YAP and FOXM1 are mediators of EGFR inhibitor resistance, and spindle proteins are therapeutic targets for this multidrug-resistant phenotype.
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“Particularly, YAP/TAZ plays a crucial role in the intrinsic and acquired resistance to inhibitors targeting RTK/MAPK pathway (24, 28–32).”
From YAP/TAZ mediates resistance to KRAS inhibitors through inhibiting proapoptosis and activating the SLC7A5/mTOR axis (2024) · cites this paper as [28]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“accumulating evidence suggests that the dysregulation of the Hippo-YAP/TAZ pathway serves as a central resistance mechanism in multiple therapies, particularly in the intrinsic and acquired resistance to RTK, RAF, or MEK inhibitors (24, 28, 29).”
From YAP/TAZ mediates resistance to KRAS inhibitors through inhibiting proapoptosis and activating the SLC7A5/mTOR axis (2024) · cites this paper as [28]
Experimental — accuracy not yet measuredIn the citing paper
“Nilsson et al. identified activation of a YAP/FOXM1 axis in EMT EGFR TKI-resistant models [91]. This was associated with dysregulation of spindle assembly checkpoint (SAC) proteins, including polo-like kinase 1, aurora kinases, and kinesin spindle protein, and rendered cells vulnerable to SAC inhibitors.”
From Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer (2021) · cites this paper as [91]
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Metadata
- Authors
- Nilsson, M. B., Sun, H., Robichaux, J., Pfeifer, M., McDermott, U., Travers, J., Diao, L., Xi, Y., Tong, P., Shen, L., Hofstad, M., Kawakami, M., Le, X., Liu, X., Fan, Y., Poteete, A., Hu, L., Negrao, M. V., Tran, H., Dmitrovsky, E., Peng, D., Gibbons, D. L., Wang, J., & Heymach, J. V.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- AstraZeneca (United Kingdom) (GB)
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Corresponding author
- Heymach, John V.
- ORCID
- Nilsson, Monique B.
- Sun, Huiying
- Robichaux, Jacqulyne
- Pfeifer, Matthias
- McDermott, Ultan
- Travers, Jon
- Diao, Lixia
- Xi, Yuanxin
- Tong, Pan
- Shen, Li
- Hofstad, Mia
- Kawakami, Masanori
- Le, Xiuning
- Liu, Xi
- Fan, Youhong
- Poteete, Alissa
- Hu, Limei
- Negrao, Marcelo V.
- Tran, Hai
- Dmitrovsky, Ethan
- Peng, David
- Gibbons, Don L.
- Wang, Jing
- Heymach, John V.
- Venue
- Science Translational Medicine
- Published
- 2020-09-02
- Volume
- 12
- Issue
- 559
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC8269000
- OpenAlex
- W3082143929
- Cited by
- 177
- References
- 74
- Citations by year
- 2026: 15 · 2025: 34 · 2024: 29 · 2023: 40 · 2022: 31 · 2021: 26 · 2020: 2
- FWCI
- 14.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Lung SPORE grant P50 CA070907, NIH CCSG (CA016672), CA016672, 1R01 CA190628)
- National Cancer Institute (HHSN261200800001E)
- LUNGevity Foundation
- University of Texas MD Anderson Cancer Center (Lung Cancer Moon Shot Program)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- epithelial-mesenchymal transition, EGFR tyrosine kinase inhibitor resistance, spindle assembly checkpoint, multidrug resistance, therapeutic vulnerabilities, non-small cell lung cancer, clinical outcomes
- MeSH terms
- Forkhead Box Protein M1, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Drug Resistance, Neoplasm, Proteomics, Cell Line, Tumor, Protein Kinase Inhibitors, Epithelial-Mesenchymal Transition, M Phase Cell Cycle Checkpoints, ErbB Receptors
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