Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Apicella et al
| Main Author: | corso, simona |
|---|---|
| Other Authors: | Apicella, Maria, Giannoni, Elisa , Fiore, Stephany, Ferrari, Karin, Fernández-Pérez , Daniel, Isella, Claudio, Granchi, Carlotta, Minutolo, Filippo, Sottile, Antonino, Comoglio, Paolo, Medico, Enzo, Pietrantonio, Filippo, Volante, Marco, Pasini, Diego, Chiarugi, Paola, Giordano, Silvia, Corso, Simona |
| Format: | Dataset |
| Terbitan: |
Mendeley
, 2018
|
| Subjects: | |
| Online Access: |
https:/data.mendeley.com/datasets/hx5jtyxtxr |
| ctrlnum |
0.17632-hx5jtyxtxr.1 |
|---|---|
| fullrecord |
<?xml version="1.0"?>
<dc><creator>corso, simona</creator><title>Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Apicella et al.</title><publisher>Mendeley</publisher><description>Microenvironment is known to influence cancer drug response and sustain resistance to therapies targeting receptor-tyrosine kinases. However if and how tumor microenvironment can be altered during treatment, contributing to resistance onset is not known. Here we show that, under prolonged treatment with tyrosine kinase inhibitors (TKIs), EGFR- or MET-addicted cancer cells displayed a metabolic shift towards increased glycolysis and lactate production. We identified secreted lactate as the key molecule able to instruct Cancer Associated Fibroblasts (CAFs) to produce Hepatocyte Growth Factor (HGF) in a NF-KB dependent manner. Increased HGF, activating MET-dependent signaling in cancer cells, sustained resistance to TKIs. Functional or pharmacological targeting of molecules involved in the lactate axis, such as lactate dehydrogenase or the lactate transporters MCT4 and MCT1, abrogated in vivo resistance, demonstrating the crucial role of this metabolite in the adaptive process.
This non-cell-autonomous, adaptive resistance mechanism was observed in NSCLC patients progressed on EGFR TKIs, demonstrating the clinical relevance of our findings and opening novel scenarios in the challenge to drug resistance.
</description><subject>Mechanism of Resistance</subject><subject>Molecular Mechanism of Cancer</subject><subject>Translational Oncology</subject><contributor>Apicella, Maria</contributor><contributor>Giannoni, Elisa </contributor><contributor>Fiore, Stephany</contributor><contributor>Ferrari, Karin</contributor><contributor>Fernández-Pérez , Daniel</contributor><contributor>Isella, Claudio</contributor><contributor>Granchi, Carlotta</contributor><contributor>Minutolo, Filippo</contributor><contributor>Sottile, Antonino</contributor><contributor>Comoglio, Paolo</contributor><contributor>Medico, Enzo</contributor><contributor>Pietrantonio, Filippo</contributor><contributor>Volante, Marco</contributor><contributor>Pasini, Diego</contributor><contributor>Chiarugi, Paola</contributor><contributor>Giordano, Silvia</contributor><contributor>Corso, Simona </contributor><type>Other:Dataset</type><identifier>10.17632/hx5jtyxtxr.1</identifier><rights>Creative Commons Attribution 4.0 International</rights><rights>http://creativecommons.org/licenses/by/4.0</rights><relation>https:/data.mendeley.com/datasets/hx5jtyxtxr</relation><date>2018-08-20T07:35:09Z</date><recordID>0.17632-hx5jtyxtxr.1</recordID></dc>
|
| format |
Other:Dataset Other |
| author |
corso, simona |
| author2 |
Apicella, Maria Giannoni, Elisa Fiore, Stephany Ferrari, Karin Fernández-Pérez , Daniel Isella, Claudio Granchi, Carlotta Minutolo, Filippo Sottile, Antonino Comoglio, Paolo Medico, Enzo Pietrantonio, Filippo Volante, Marco Pasini, Diego Chiarugi, Paola Giordano, Silvia Corso, Simona |
| title |
Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Apicella et al |
| publisher |
Mendeley |
| publishDate |
2018 |
| topic |
Mechanism of Resistance Molecular Mechanism of Cancer Translational Oncology |
| url |
https:/data.mendeley.com/datasets/hx5jtyxtxr |
| contents |
Microenvironment is known to influence cancer drug response and sustain resistance to therapies targeting receptor-tyrosine kinases. However if and how tumor microenvironment can be altered during treatment, contributing to resistance onset is not known. Here we show that, under prolonged treatment with tyrosine kinase inhibitors (TKIs), EGFR- or MET-addicted cancer cells displayed a metabolic shift towards increased glycolysis and lactate production. We identified secreted lactate as the key molecule able to instruct Cancer Associated Fibroblasts (CAFs) to produce Hepatocyte Growth Factor (HGF) in a NF-KB dependent manner. Increased HGF, activating MET-dependent signaling in cancer cells, sustained resistance to TKIs. Functional or pharmacological targeting of molecules involved in the lactate axis, such as lactate dehydrogenase or the lactate transporters MCT4 and MCT1, abrogated in vivo resistance, demonstrating the crucial role of this metabolite in the adaptive process.
This non-cell-autonomous, adaptive resistance mechanism was observed in NSCLC patients progressed on EGFR TKIs, demonstrating the clinical relevance of our findings and opening novel scenarios in the challenge to drug resistance.
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IOS7969.0.17632-hx5jtyxtxr.1 |
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Universitas Islam Indragiri |
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onesearch.perpusnas.go.id |
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804 |
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library:university library |
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Teknologi Pangan UNISI |
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2816 |
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INDRAGIRI HILIR |
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RIAU |
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