Data from MET–GRB2 Signaling-Associated Complexes Correlate with Oncogenic MET Signaling and Sensitivity to MET Kinase Inhibitors Article Swipe
Matthew A. Smith
,
Thomas Licata
,
Aliya Lakhani
,
Marileila Garcia
,
Hans‐Ulrich Schildhaus
,
Vincent Vuaroqueaux
,
Balázs Halmos
,
Alain Borczuk
,
Y. Ann Chen
,
Ben Creelan
,
Theresa A. Boyle
,
Eric B. Haura
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.c.6525692
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.c.6525692
Purpose: Targeting MET in cancer is hampered by lack of diagnostics that accurately reflect high MET signaling and dependence. We hypothesized that assays reflecting MET signaling associated protein complexes could redefine tumors dependent on MET and could add additional precision beyond genomic assessments.Experimental Design: We used biochemical approaches, cellular viability studies, and proximity ligation assays to assess MET dependence. We examined MET signaling complexes in lung cancer patient specimens (N = 406) and patient-derived xenograft (PDX) models of solid tumors (N = 308). We evaluated response to crizotinib in a MET-amplified cohort of PDX models of lung cancer (N = 6) and provide a case report of a lung cancer patient harboring a Δexon14 MET splice variant.Results: We found the interaction of MET with the adaptor protein GRB2 is necessary for oncogenic survival signaling by MET. MET-GRB2 complexes were identified only within MET-amplified PDX models and patient specimens but exhibit substantial variability. Lack of MET-GRB2 complexes was associated with lack of response to MET TKI in cell lines and PDX models. Presence of MET-GRB2 complexes can further subtype tumors with Δexon14 MET splice variants. Presence of these complexes correlated with response to crizotinib in one patient with Δexon14 MET lacking MET gene amplification.Conclusions: Proximity assays measuring MET-GRB2 signaling complexes provide novel insights into MET-mediated signaling and could complement current clinical genomics-based assay platforms. Clin Cancer Res; 23(22); 7084–96. ©2017 AACR.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/1078-0432.c.6525692
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4361945791Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/1078-0432.c.6525692Digital Object Identifier
- Title
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Data from MET–GRB2 Signaling-Associated Complexes Correlate with Oncogenic MET Signaling and Sensitivity to MET Kinase InhibitorsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-03-31Full publication date if available
- Authors
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Matthew A. Smith, Thomas Licata, Aliya Lakhani, Marileila Garcia, Hans‐Ulrich Schildhaus, Vincent Vuaroqueaux, Balázs Halmos, Alain Borczuk, Y. Ann Chen, Ben Creelan, Theresa A. Boyle, Eric B. HauraList of authors in order
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https://doi.org/10.1158/1078-0432.c.6525692Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1158/1078-0432.c.6525692Direct OA link when available
- Concepts
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Cancer research, Crizotinib, Signal transducing adaptor protein, GRB2, Signal transduction, Cancer, Lung cancer, Biology, Molecular biology, Medicine, Chemistry, Internal medicine, Genetics, Malignant pleural effusionTop concepts (fields/topics) attached by OpenAlex
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.signaling | 16, 25, 62, 133, 207, 214 |
| abstract_inverted_index.specimens | 68, 147 |
| abstract_inverted_index.variants. | 183 |
| abstract_inverted_index.viability | 49 |
| abstract_inverted_index.xenograft | 74 |
| abstract_inverted_index.7084–96. | 227 |
| abstract_inverted_index.accurately | 12 |
| abstract_inverted_index.additional | 38 |
| abstract_inverted_index.associated | 26, 157 |
| abstract_inverted_index.complement | 217 |
| abstract_inverted_index.correlated | 188 |
| abstract_inverted_index.crizotinib | 87, 192 |
| abstract_inverted_index.identified | 139 |
| abstract_inverted_index.platforms. | 222 |
| abstract_inverted_index.reflecting | 23 |
| abstract_inverted_index.approaches, | 47 |
| abstract_inverted_index.biochemical | 46 |
| abstract_inverted_index.dependence. | 18, 58 |
| abstract_inverted_index.diagnostics | 10 |
| abstract_inverted_index.interaction | 120 |
| abstract_inverted_index.substantial | 150 |
| abstract_inverted_index.MET-mediated | 213 |
| abstract_inverted_index.hypothesized | 20 |
| abstract_inverted_index.variability. | 151 |
| abstract_inverted_index.<i>Clin | 223 |
| abstract_inverted_index.genomics-based | 220 |
| abstract_inverted_index.patient-derived | 73 |
| abstract_inverted_index.Design:</b> | 43 |
| abstract_inverted_index.(<i>N</i> | 69, 80, 98 |
| abstract_inverted_index.<i>MET</i> | 114, 181 |
| abstract_inverted_index.<i>MET</i>-amplified | 90, 142 |
| abstract_inverted_index.AACR</i>.</p></div> | 229 |
| abstract_inverted_index.assessments.</p><p><b>Experimental | 42 |
| abstract_inverted_index.variant.</p><p><b>Results:</b> | 116 |
| abstract_inverted_index.<div>Abstract<p><b>Purpose:</b> | 0 |
| abstract_inverted_index.amplification.</p><p><b>Conclusions:</b> | 202 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 12 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.6100000143051147 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.12090259 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |