MET overexpression and activation favors invasiveness in a model of anaplastic thyroid cancer
In thyroid cancers, MET receptor overexpression has been associated with higher risk of metastatic progression. In this study, it was shown that the anaplastic thyroid cancer (ATC)-derived TTA1 cell line overexpressed MET. By using FISH and relative quantification by qPCR, it was demonstrated that t...
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creator | Garcia, Cyril Buffet, Camille El Khattabi, Laila Rizk-Rabin, Marthe Perlemoine, Karine Ragazzon, Bruno Bertherat, Jérôme Cormier, Françoise Groussin, Lionel |
description | In thyroid cancers, MET receptor overexpression has been associated with higher risk of metastatic progression. In this study, it was shown that the anaplastic thyroid cancer (ATC)-derived TTA1 cell line overexpressed MET. By using FISH and relative quantification by qPCR, it was demonstrated that this overexpression resulted from a
amplification with more than 20 copies. As expected, MET overexpression led to its constitutive activation and upregulated signaling towards the MAPK, PI3K/AKT, STAT3 and NF-κB pathways. Since the usual feature of
-amplified cell lines is the "MET addiction" for their cell proliferation, the effect of the highly selective ATP competitive MET inhibitor PHA665752 was analyzed. While PHA665752 strongly inhibited the MAPK pathway, it did not reduce cell proliferation in TTA1 cells (IC
= 4100 nM). This resistance to PHA665752 of the TTA1 cell line was demonstrated to be related to EGFR-MET functional cross-talk and PI3K/AKT and NF-κB signaling. Nevertheless, PHA665752 suppressed the anchorage-independent growth capacity of the TTA1 cell line and reduced cell migration and invasion in a transwell assay. The role of activated MET in these neoplastic properties of the TTA1 cells was also proved with si-MET-RNA targeting. Thus, this work highlights the TTA1 cell line as the first model of
amplification in an ATC cell line, which leads to MET constitutive activation and underlies its neoplastic properties. Besides being a useful model for MET inhibitors screening, the TTA1 cell line also supports the argument for searching for
amplification in ATC, as it could have therapeutic implications. |
doi_str_mv | 10.18632/oncotarget.26798 |
format | Article |
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amplification with more than 20 copies. As expected, MET overexpression led to its constitutive activation and upregulated signaling towards the MAPK, PI3K/AKT, STAT3 and NF-κB pathways. Since the usual feature of
-amplified cell lines is the "MET addiction" for their cell proliferation, the effect of the highly selective ATP competitive MET inhibitor PHA665752 was analyzed. While PHA665752 strongly inhibited the MAPK pathway, it did not reduce cell proliferation in TTA1 cells (IC
= 4100 nM). This resistance to PHA665752 of the TTA1 cell line was demonstrated to be related to EGFR-MET functional cross-talk and PI3K/AKT and NF-κB signaling. Nevertheless, PHA665752 suppressed the anchorage-independent growth capacity of the TTA1 cell line and reduced cell migration and invasion in a transwell assay. The role of activated MET in these neoplastic properties of the TTA1 cells was also proved with si-MET-RNA targeting. Thus, this work highlights the TTA1 cell line as the first model of
amplification in an ATC cell line, which leads to MET constitutive activation and underlies its neoplastic properties. Besides being a useful model for MET inhibitors screening, the TTA1 cell line also supports the argument for searching for
amplification in ATC, as it could have therapeutic implications.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.26798</identifier><identifier>PMID: 31040922</identifier><language>eng</language><publisher>United States: Impact journals</publisher><subject>Life Sciences ; Research Paper</subject><ispartof>Oncotarget, 2019-03, Vol.10 (23), p.2320-2334</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright: © 2019 Garcia et al. 2019</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4148-cf6385ceb47312a6812a1260a33499e788744dd2ac89034aa53270b5b25285ca3</citedby><cites>FETCH-LOGICAL-c4148-cf6385ceb47312a6812a1260a33499e788744dd2ac89034aa53270b5b25285ca3</cites><orcidid>0000-0001-9476-4973 ; 0000-0002-6904-5122</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481343/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481343/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31040922$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02325867$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Garcia, Cyril</creatorcontrib><creatorcontrib>Buffet, Camille</creatorcontrib><creatorcontrib>El Khattabi, Laila</creatorcontrib><creatorcontrib>Rizk-Rabin, Marthe</creatorcontrib><creatorcontrib>Perlemoine, Karine</creatorcontrib><creatorcontrib>Ragazzon, Bruno</creatorcontrib><creatorcontrib>Bertherat, Jérôme</creatorcontrib><creatorcontrib>Cormier, Françoise</creatorcontrib><creatorcontrib>Groussin, Lionel</creatorcontrib><title>MET overexpression and activation favors invasiveness in a model of anaplastic thyroid cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>In thyroid cancers, MET receptor overexpression has been associated with higher risk of metastatic progression. In this study, it was shown that the anaplastic thyroid cancer (ATC)-derived TTA1 cell line overexpressed MET. By using FISH and relative quantification by qPCR, it was demonstrated that this overexpression resulted from a
amplification with more than 20 copies. As expected, MET overexpression led to its constitutive activation and upregulated signaling towards the MAPK, PI3K/AKT, STAT3 and NF-κB pathways. Since the usual feature of
-amplified cell lines is the "MET addiction" for their cell proliferation, the effect of the highly selective ATP competitive MET inhibitor PHA665752 was analyzed. While PHA665752 strongly inhibited the MAPK pathway, it did not reduce cell proliferation in TTA1 cells (IC
= 4100 nM). This resistance to PHA665752 of the TTA1 cell line was demonstrated to be related to EGFR-MET functional cross-talk and PI3K/AKT and NF-κB signaling. Nevertheless, PHA665752 suppressed the anchorage-independent growth capacity of the TTA1 cell line and reduced cell migration and invasion in a transwell assay. The role of activated MET in these neoplastic properties of the TTA1 cells was also proved with si-MET-RNA targeting. Thus, this work highlights the TTA1 cell line as the first model of
amplification in an ATC cell line, which leads to MET constitutive activation and underlies its neoplastic properties. Besides being a useful model for MET inhibitors screening, the TTA1 cell line also supports the argument for searching for
amplification in ATC, as it could have therapeutic implications.</description><subject>Life Sciences</subject><subject>Research Paper</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkUtPAyEUhYnRqFF_gBvDUhdVnjOwMTGmPpIaN7o05JZhLGYKFaYT_fei9c3iwoXzHXJzENqn5JiqirOTGGzsIT26_phVtVZraJtqoUdMSr7-67yF9nJ-ImVJUSumN9EWp0QQzdg2ergZ3-E4uOReFsnl7GPAEBoMtvcD9O9tC0NMGfswQPaDC0VVGgx4HhvX4dgWABYd5N5b3M9eU_QNthCsS7too4Uuu73PfQfdX4zvzq9Gk9vL6_OzycgKKtTIthVX0rqpqDllUKlSKKsIcC60drVStRBNw8AqTbgAkJzVZCqnTLLCAd9BpyvfxXI6d411oU_QmUXyc0ivJoI3f1-Cn5nHOJhKKMoFLwZHK4PZP-zqbGLe7wjjTKqqHmjRHn5-luLz0uXezH22rusguLjMhjGqOOFa1kVKV1KbYs7Jtd_elJiPFM1PiuYjxcIc_J7lm_jKjL8BDqKbjA</recordid><startdate>20190319</startdate><enddate>20190319</enddate><creator>Garcia, Cyril</creator><creator>Buffet, Camille</creator><creator>El Khattabi, Laila</creator><creator>Rizk-Rabin, Marthe</creator><creator>Perlemoine, Karine</creator><creator>Ragazzon, Bruno</creator><creator>Bertherat, Jérôme</creator><creator>Cormier, Françoise</creator><creator>Groussin, Lionel</creator><general>Impact journals</general><general>Impact Journals LLC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9476-4973</orcidid><orcidid>https://orcid.org/0000-0002-6904-5122</orcidid></search><sort><creationdate>20190319</creationdate><title>MET overexpression and activation favors invasiveness in a model of anaplastic thyroid cancer</title><author>Garcia, Cyril ; Buffet, Camille ; El Khattabi, Laila ; Rizk-Rabin, Marthe ; Perlemoine, Karine ; Ragazzon, Bruno ; Bertherat, Jérôme ; Cormier, Françoise ; Groussin, Lionel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4148-cf6385ceb47312a6812a1260a33499e788744dd2ac89034aa53270b5b25285ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Life Sciences</topic><topic>Research Paper</topic><toplevel>online_resources</toplevel><creatorcontrib>Garcia, Cyril</creatorcontrib><creatorcontrib>Buffet, Camille</creatorcontrib><creatorcontrib>El Khattabi, Laila</creatorcontrib><creatorcontrib>Rizk-Rabin, Marthe</creatorcontrib><creatorcontrib>Perlemoine, Karine</creatorcontrib><creatorcontrib>Ragazzon, Bruno</creatorcontrib><creatorcontrib>Bertherat, Jérôme</creatorcontrib><creatorcontrib>Cormier, Françoise</creatorcontrib><creatorcontrib>Groussin, Lionel</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garcia, Cyril</au><au>Buffet, Camille</au><au>El Khattabi, Laila</au><au>Rizk-Rabin, Marthe</au><au>Perlemoine, Karine</au><au>Ragazzon, Bruno</au><au>Bertherat, Jérôme</au><au>Cormier, Françoise</au><au>Groussin, Lionel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MET overexpression and activation favors invasiveness in a model of anaplastic thyroid cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2019-03-19</date><risdate>2019</risdate><volume>10</volume><issue>23</issue><spage>2320</spage><epage>2334</epage><pages>2320-2334</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>In thyroid cancers, MET receptor overexpression has been associated with higher risk of metastatic progression. In this study, it was shown that the anaplastic thyroid cancer (ATC)-derived TTA1 cell line overexpressed MET. By using FISH and relative quantification by qPCR, it was demonstrated that this overexpression resulted from a
amplification with more than 20 copies. As expected, MET overexpression led to its constitutive activation and upregulated signaling towards the MAPK, PI3K/AKT, STAT3 and NF-κB pathways. Since the usual feature of
-amplified cell lines is the "MET addiction" for their cell proliferation, the effect of the highly selective ATP competitive MET inhibitor PHA665752 was analyzed. While PHA665752 strongly inhibited the MAPK pathway, it did not reduce cell proliferation in TTA1 cells (IC
= 4100 nM). This resistance to PHA665752 of the TTA1 cell line was demonstrated to be related to EGFR-MET functional cross-talk and PI3K/AKT and NF-κB signaling. Nevertheless, PHA665752 suppressed the anchorage-independent growth capacity of the TTA1 cell line and reduced cell migration and invasion in a transwell assay. The role of activated MET in these neoplastic properties of the TTA1 cells was also proved with si-MET-RNA targeting. Thus, this work highlights the TTA1 cell line as the first model of
amplification in an ATC cell line, which leads to MET constitutive activation and underlies its neoplastic properties. Besides being a useful model for MET inhibitors screening, the TTA1 cell line also supports the argument for searching for
amplification in ATC, as it could have therapeutic implications.</abstract><cop>United States</cop><pub>Impact journals</pub><pmid>31040922</pmid><doi>10.18632/oncotarget.26798</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-9476-4973</orcidid><orcidid>https://orcid.org/0000-0002-6904-5122</orcidid><oa>free_for_read</oa></addata></record> |
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title | MET overexpression and activation favors invasiveness in a model of anaplastic thyroid cancer |
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