CLIP170 inhibits the metastasis and EMT of papillary thyroid cancer through the TGF-β pathway
Metastasis poses a significant challenge in combating tumors. Even in papillary thyroid cancer (PTC), which typically exhibits a favorable prognosis, high recurrence rates are attributed to metastasis. Cytoplasmic linker protein 170 (CLIP170) functions as a classical microtubule plus-end tracking pr...
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| Veröffentlicht in: | Medical oncology (Northwood, London, England) London, England), 2024-05, Vol.41 (6), p.137, Article 137 |
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| creator | Ma, Binyuan Xu, Yaxin Gao, Hongwei Yang, Yinggui Pan, Yunyan You, Chongge |
| description | Metastasis poses a significant challenge in combating tumors. Even in papillary thyroid cancer (PTC), which typically exhibits a favorable prognosis, high recurrence rates are attributed to metastasis. Cytoplasmic linker protein 170 (CLIP170) functions as a classical microtubule plus-end tracking protein (+TIP) and has shown close association with cell migration. Nevertheless, the specific impact of CLIP170 on PTC cells remains to be elucidated. Our analysis of the GEO and TCGA databases unveiled an association between CLIP170 and the progression of PTC. To explore the impact of CLIP170 on PTC cells, we conducted various assays. We evaluated its effects through CCK-8, wound healing assay, and transwell assay after knocking down CLIP170. Additionally, the influence of CLIP170 on the cellular actin structure was examined via immunofluorescence; we further investigated the molecular expressions of epithelial-mesenchymal transition (EMT) and the transforming growth factor-β (TGF-β) signaling pathways through Western blotting and RT-qPCR. These findings were substantiated through an in vivo nude mouse model of lung metastasis. We observed a decreased expression of CLIP170 in PTC in contrast to normal thyroid tissue. Functionally, the knockdown of CLIP170 (CLIP170
KD
) notably enhanced the metastatic potential and EMT of PTC cells, both in vitro and in vivo. Mechanistically, CLIP170
KD
triggered the activation of the TGF-β pathway, subsequently promoting tumor cell migration, invasion, and EMT. Remarkably, the TGF-β inhibitor LY2157299 effectively countered TGF-β activity and significantly reversed tumor metastasis and EMT induced by CLIP170 knockdown. In summary, these findings collectively propose CLIP170 as a promising therapeutic target to mitigate metastatic tendencies in PTC. |
| doi_str_mv | 10.1007/s12032-024-02355-z |
| format | Article |
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KD
) notably enhanced the metastatic potential and EMT of PTC cells, both in vitro and in vivo. Mechanistically, CLIP170
KD
triggered the activation of the TGF-β pathway, subsequently promoting tumor cell migration, invasion, and EMT. Remarkably, the TGF-β inhibitor LY2157299 effectively countered TGF-β activity and significantly reversed tumor metastasis and EMT induced by CLIP170 knockdown. In summary, these findings collectively propose CLIP170 as a promising therapeutic target to mitigate metastatic tendencies in PTC.</description><identifier>ISSN: 1559-131X</identifier><identifier>ISSN: 1357-0560</identifier><identifier>EISSN: 1559-131X</identifier><identifier>DOI: 10.1007/s12032-024-02355-z</identifier><identifier>PMID: 38705933</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Cell adhesion & migration ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Female ; Hematology ; Humans ; Internal Medicine ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lung Neoplasms - secondary ; Male ; Medicine ; Medicine & Public Health ; Metastasis ; Mice ; Mice, Nude ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; Neoplasm Metastasis ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Oncology ; Original Paper ; Pathology ; Signal Transduction ; Thyroid cancer ; Thyroid Cancer, Papillary - genetics ; Thyroid Cancer, Papillary - metabolism ; Thyroid Cancer, Papillary - pathology ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - metabolism ; Thyroid Neoplasms - pathology ; Transforming Growth Factor beta - metabolism</subject><ispartof>Medical oncology (Northwood, London, England), 2024-05, Vol.41 (6), p.137, Article 137</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-83ddda9c4b9e340f43ca6d8893482ade681bf950f6c7ae165a4e0ead6006d1423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12032-024-02355-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12032-024-02355-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38705933$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Binyuan</creatorcontrib><creatorcontrib>Xu, Yaxin</creatorcontrib><creatorcontrib>Gao, Hongwei</creatorcontrib><creatorcontrib>Yang, Yinggui</creatorcontrib><creatorcontrib>Pan, Yunyan</creatorcontrib><creatorcontrib>You, Chongge</creatorcontrib><title>CLIP170 inhibits the metastasis and EMT of papillary thyroid cancer through the TGF-β pathway</title><title>Medical oncology (Northwood, London, England)</title><addtitle>Med Oncol</addtitle><addtitle>Med Oncol</addtitle><description>Metastasis poses a significant challenge in combating tumors. Even in papillary thyroid cancer (PTC), which typically exhibits a favorable prognosis, high recurrence rates are attributed to metastasis. Cytoplasmic linker protein 170 (CLIP170) functions as a classical microtubule plus-end tracking protein (+TIP) and has shown close association with cell migration. Nevertheless, the specific impact of CLIP170 on PTC cells remains to be elucidated. Our analysis of the GEO and TCGA databases unveiled an association between CLIP170 and the progression of PTC. To explore the impact of CLIP170 on PTC cells, we conducted various assays. We evaluated its effects through CCK-8, wound healing assay, and transwell assay after knocking down CLIP170. Additionally, the influence of CLIP170 on the cellular actin structure was examined via immunofluorescence; we further investigated the molecular expressions of epithelial-mesenchymal transition (EMT) and the transforming growth factor-β (TGF-β) signaling pathways through Western blotting and RT-qPCR. These findings were substantiated through an in vivo nude mouse model of lung metastasis. We observed a decreased expression of CLIP170 in PTC in contrast to normal thyroid tissue. Functionally, the knockdown of CLIP170 (CLIP170
KD
) notably enhanced the metastatic potential and EMT of PTC cells, both in vitro and in vivo. Mechanistically, CLIP170
KD
triggered the activation of the TGF-β pathway, subsequently promoting tumor cell migration, invasion, and EMT. Remarkably, the TGF-β inhibitor LY2157299 effectively countered TGF-β activity and significantly reversed tumor metastasis and EMT induced by CLIP170 knockdown. In summary, these findings collectively propose CLIP170 as a promising therapeutic target to mitigate metastatic tendencies in PTC.</description><subject>Animals</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - secondary</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Pathology</subject><subject>Signal Transduction</subject><subject>Thyroid cancer</subject><subject>Thyroid Cancer, Papillary - genetics</subject><subject>Thyroid Cancer, Papillary - metabolism</subject><subject>Thyroid Cancer, Papillary - pathology</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - metabolism</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>1559-131X</issn><issn>1357-0560</issn><issn>1559-131X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKAzEUhoMotlZfwIUMuHEzenKby1JKWwsVXVRwZchMMp0p7UxNZpD2sXwQn8m0Uy-4EHJIDvn-Pyc_QucYrjFAeGMxAUp8IMwV5dzfHKAu5jz2McXPh7_OHXRi7RyAYE7iY9ShUQg8prSLXvqT8SMOwSvKvEiK2np1rr2lrqV1q7CeLJU3uJ96Veat5KpYLKRZO2ZtqkJ5qSxTbVxrqmaW76TT0dD_eHdsnb_J9Sk6yuTC6rP93kNPw8G0f-dPHkbj_u3ETykJaj-iSikZpyyJNWWQMZrKQEVRTFlEpNJBhJMs5pAFaSg1DrhkGrRUAUCgMCO0h65a35WpXhtta7EsbKrdtKWuGisocIdxxgKHXv5B51VjSjfdloKQc0Kpo0hLpaay1uhMrEyxdH8XGMQ2fdGmL1z6Ype-2DjRxd66SZZafUu-4nYAbQHrrsqZNj9v_2P7CfDfj7c</recordid><startdate>20240505</startdate><enddate>20240505</enddate><creator>Ma, Binyuan</creator><creator>Xu, Yaxin</creator><creator>Gao, Hongwei</creator><creator>Yang, Yinggui</creator><creator>Pan, Yunyan</creator><creator>You, Chongge</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20240505</creationdate><title>CLIP170 inhibits the metastasis and EMT of papillary thyroid cancer through the TGF-β pathway</title><author>Ma, Binyuan ; Xu, Yaxin ; Gao, Hongwei ; Yang, Yinggui ; Pan, Yunyan ; You, Chongge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-83ddda9c4b9e340f43ca6d8893482ade681bf950f6c7ae165a4e0ead6006d1423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - secondary</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>Signal Transduction</topic><topic>Thyroid cancer</topic><topic>Thyroid Cancer, Papillary - genetics</topic><topic>Thyroid Cancer, Papillary - metabolism</topic><topic>Thyroid Cancer, Papillary - pathology</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - metabolism</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Binyuan</creatorcontrib><creatorcontrib>Xu, Yaxin</creatorcontrib><creatorcontrib>Gao, Hongwei</creatorcontrib><creatorcontrib>Yang, Yinggui</creatorcontrib><creatorcontrib>Pan, Yunyan</creatorcontrib><creatorcontrib>You, Chongge</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Medical oncology (Northwood, London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Binyuan</au><au>Xu, Yaxin</au><au>Gao, Hongwei</au><au>Yang, Yinggui</au><au>Pan, Yunyan</au><au>You, Chongge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CLIP170 inhibits the metastasis and EMT of papillary thyroid cancer through the TGF-β pathway</atitle><jtitle>Medical oncology (Northwood, London, England)</jtitle><stitle>Med Oncol</stitle><addtitle>Med Oncol</addtitle><date>2024-05-05</date><risdate>2024</risdate><volume>41</volume><issue>6</issue><spage>137</spage><pages>137-</pages><artnum>137</artnum><issn>1559-131X</issn><issn>1357-0560</issn><eissn>1559-131X</eissn><abstract>Metastasis poses a significant challenge in combating tumors. Even in papillary thyroid cancer (PTC), which typically exhibits a favorable prognosis, high recurrence rates are attributed to metastasis. Cytoplasmic linker protein 170 (CLIP170) functions as a classical microtubule plus-end tracking protein (+TIP) and has shown close association with cell migration. Nevertheless, the specific impact of CLIP170 on PTC cells remains to be elucidated. Our analysis of the GEO and TCGA databases unveiled an association between CLIP170 and the progression of PTC. To explore the impact of CLIP170 on PTC cells, we conducted various assays. We evaluated its effects through CCK-8, wound healing assay, and transwell assay after knocking down CLIP170. Additionally, the influence of CLIP170 on the cellular actin structure was examined via immunofluorescence; we further investigated the molecular expressions of epithelial-mesenchymal transition (EMT) and the transforming growth factor-β (TGF-β) signaling pathways through Western blotting and RT-qPCR. These findings were substantiated through an in vivo nude mouse model of lung metastasis. We observed a decreased expression of CLIP170 in PTC in contrast to normal thyroid tissue. Functionally, the knockdown of CLIP170 (CLIP170
KD
) notably enhanced the metastatic potential and EMT of PTC cells, both in vitro and in vivo. Mechanistically, CLIP170
KD
triggered the activation of the TGF-β pathway, subsequently promoting tumor cell migration, invasion, and EMT. Remarkably, the TGF-β inhibitor LY2157299 effectively countered TGF-β activity and significantly reversed tumor metastasis and EMT induced by CLIP170 knockdown. In summary, these findings collectively propose CLIP170 as a promising therapeutic target to mitigate metastatic tendencies in PTC.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38705933</pmid><doi>10.1007/s12032-024-02355-z</doi></addata></record> |
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| subjects | Animals Cell adhesion & migration Cell Line, Tumor Cell Movement Epithelial-Mesenchymal Transition Female Hematology Humans Internal Medicine Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Lung Neoplasms - secondary Male Medicine Medicine & Public Health Metastasis Mice Mice, Nude Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - metabolism Neoplasm Metastasis Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Oncology Original Paper Pathology Signal Transduction Thyroid cancer Thyroid Cancer, Papillary - genetics Thyroid Cancer, Papillary - metabolism Thyroid Cancer, Papillary - pathology Thyroid Neoplasms - genetics Thyroid Neoplasms - metabolism Thyroid Neoplasms - pathology Transforming Growth Factor beta - metabolism |
| title | CLIP170 inhibits the metastasis and EMT of papillary thyroid cancer through the TGF-β pathway |
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