Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression
Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexp...
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| Veröffentlicht in: | PLoS genetics 2019-10, Vol.15 (10), p.e1008439-e1008439 |
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| creator | Malvi, Parmanand Janostiak, Radoslav Nagarajan, Arvindhan Cai, Guoping Wajapeyee, Narendra |
| description | Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy. |
| doi_str_mv | 10.1371/journal.pgen.1008439 |
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Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1008439</identifier><identifier>PMID: 31589613</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adenocarcinoma of Lung - genetics ; Adenocarcinoma of Lung - mortality ; Adenocarcinoma of Lung - pathology ; Adult ; Aged ; Animals ; Biochemistry ; Biology and Life Sciences ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Cancer metastasis ; Cancer recurrence ; Cell adhesion & migration ; Cell culture ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; Criminal investigation ; Datasets as Topic ; DNA-Binding Proteins - metabolism ; Ectopic expression ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genes ; Genetic aspects ; Growth ; Growth Differentiation Factor 15 - metabolism ; Guanosine triphosphatases ; Humans ; Kinases ; Lung - pathology ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Male ; MAP kinase ; Medical prognosis ; Medicine and Health Sciences ; Metabolism ; Metastases ; Metastasis ; Mice ; Middle Aged ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - pathology ; Pathology ; Patients ; Prognosis ; Protein expression ; Proteins ; Recurrence (Disease) ; Research and Analysis Methods ; Scientific equipment industry ; Survival Analysis ; Thymidine ; Thymidine kinase ; Thymidine Kinase - genetics ; Thymidine Kinase - metabolism ; Trametinib ; Transcription (Genetics) ; Transcription Factors - metabolism ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>PLoS genetics, 2019-10, Vol.15 (10), p.e1008439-e1008439</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Malvi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Malvi et al 2019 Malvi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c777t-6721c1946ffede08cdbadbb2a69fd9f4410b94e42e657372ccdd2aa35a9286803</citedby><cites>FETCH-LOGICAL-c777t-6721c1946ffede08cdbadbb2a69fd9f4410b94e42e657372ccdd2aa35a9286803</cites><orcidid>0000-0003-3306-349X ; 0000-0002-6602-9389</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/PMC6797230/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797230/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31589613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hunter, Kent W.</contributor><creatorcontrib>Malvi, Parmanand</creatorcontrib><creatorcontrib>Janostiak, Radoslav</creatorcontrib><creatorcontrib>Nagarajan, Arvindhan</creatorcontrib><creatorcontrib>Cai, Guoping</creatorcontrib><creatorcontrib>Wajapeyee, Narendra</creatorcontrib><title>Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma of Lung - genetics</subject><subject>Adenocarcinoma of Lung - mortality</subject><subject>Adenocarcinoma of Lung - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer metastasis</subject><subject>Cancer recurrence</subject><subject>Cell adhesion & migration</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Criminal investigation</subject><subject>Datasets as Topic</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Ectopic expression</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Growth</subject><subject>Growth Differentiation Factor 15 - metabolism</subject><subject>Guanosine triphosphatases</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lung - pathology</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Pathology</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Recurrence (Disease)</subject><subject>Research and Analysis Methods</subject><subject>Scientific equipment industry</subject><subject>Survival Analysis</subject><subject>Thymidine</subject><subject>Thymidine kinase</subject><subject>Thymidine Kinase - genetics</subject><subject>Thymidine Kinase - metabolism</subject><subject>Trametinib</subject><subject>Transcription (Genetics)</subject><subject>Transcription Factors - metabolism</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVk11vFCEUhidGY2v1HxglMTF6sSsMzDBzY9JUWzfZ2MSvW8LAmVnqDKzAaPffy7jbZtf0QsMFBJ73PecAJ8ueEjwnlJM3V270VvbzdQd2TjCuGK3vZcekKOiMM8zu762PskchXGFMi6rmD7MjStKiJPQ4G5YuBORaFFebwWhjAX03VgZABBm7Mo2JAfWj7ZCSVoFHnXe_4gpJq9EAUYYoo1FIxuhNM0YIqNkgD3pUJmku3p2TAsH12kMIxtnH2YNW9gGe7OaT7Ov5-y9nH2bLy4vF2elypjjncVbynChSs7JtQQOulG6kbppclnWr65YxgpuaAcuhLDjluVJa51LSQtZ5VVaYnmTPt77r3gWxu6kgckpYTVlO60QstoR28kqsvRmk3wgnjfiz4XwnpE-V9SBKoCUvmypnGjOguKoYriStFJCmriRLXm930cZmAK3ARi_7A9PDE2tWonM_RclrntMp3Vc7A-9-jBCiGExQ0PfSghunvHHOOMmLKe8Xf6F3V7ejOpkKMLZ1Ka6aTMVpiXmZzMiU9_wOKg0Ng1HOQmvS_oHg9YEgMRGuYyfHEMTi86f_YD_-O3v57ZB9uceuQPZxFVw_xvS9wiHItqDy6Yt7aG8fhGAxddDNzYmpg8Sug5Ls2f5j3opuWob-BvEKFQU</recordid><startdate>20191007</startdate><enddate>20191007</enddate><creator>Malvi, Parmanand</creator><creator>Janostiak, Radoslav</creator><creator>Nagarajan, Arvindhan</creator><creator>Cai, Guoping</creator><creator>Wajapeyee, Narendra</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3306-349X</orcidid><orcidid>https://orcid.org/0000-0002-6602-9389</orcidid></search><sort><creationdate>20191007</creationdate><title>Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression</title><author>Malvi, Parmanand ; Janostiak, Radoslav ; Nagarajan, Arvindhan ; Cai, Guoping ; Wajapeyee, Narendra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c777t-6721c1946ffede08cdbadbb2a69fd9f4410b94e42e657372ccdd2aa35a9286803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma of Lung - genetics</topic><topic>Adenocarcinoma of Lung - mortality</topic><topic>Adenocarcinoma of Lung - pathology</topic><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer metastasis</topic><topic>Cancer recurrence</topic><topic>Cell adhesion & migration</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Criminal investigation</topic><topic>Datasets as Topic</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Ectopic expression</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Growth</topic><topic>Growth Differentiation Factor 15 - metabolism</topic><topic>Guanosine triphosphatases</topic><topic>Humans</topic><topic>Kinases</topic><topic>Lung - pathology</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Pathology</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Recurrence (Disease)</topic><topic>Research and Analysis Methods</topic><topic>Scientific equipment industry</topic><topic>Survival Analysis</topic><topic>Thymidine</topic><topic>Thymidine kinase</topic><topic>Thymidine Kinase - genetics</topic><topic>Thymidine Kinase - metabolism</topic><topic>Trametinib</topic><topic>Transcription (Genetics)</topic><topic>Transcription Factors - metabolism</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Malvi, Parmanand</creatorcontrib><creatorcontrib>Janostiak, Radoslav</creatorcontrib><creatorcontrib>Nagarajan, Arvindhan</creatorcontrib><creatorcontrib>Cai, Guoping</creatorcontrib><creatorcontrib>Wajapeyee, Narendra</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Malvi, Parmanand</au><au>Janostiak, Radoslav</au><au>Nagarajan, Arvindhan</au><au>Cai, Guoping</au><au>Wajapeyee, Narendra</au><au>Hunter, Kent W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2019-10-07</date><risdate>2019</risdate><volume>15</volume><issue>10</issue><spage>e1008439</spage><epage>e1008439</epage><pages>e1008439-e1008439</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31589613</pmid><doi>10.1371/journal.pgen.1008439</doi><orcidid>https://orcid.org/0000-0003-3306-349X</orcidid><orcidid>https://orcid.org/0000-0002-6602-9389</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - mortality Adenocarcinoma of Lung - pathology Adult Aged Animals Biochemistry Biology and Life Sciences Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Cancer metastasis Cancer recurrence Cell adhesion & migration Cell culture Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Criminal investigation Datasets as Topic DNA-Binding Proteins - metabolism Ectopic expression Female Gene expression Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Genes Genetic aspects Growth Growth Differentiation Factor 15 - metabolism Guanosine triphosphatases Humans Kinases Lung - pathology Lung cancer Lung Neoplasms - genetics Lung Neoplasms - mortality Lung Neoplasms - pathology Male MAP kinase Medical prognosis Medicine and Health Sciences Metabolism Metastases Metastasis Mice Middle Aged Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - pathology Pathology Patients Prognosis Protein expression Proteins Recurrence (Disease) Research and Analysis Methods Scientific equipment industry Survival Analysis Thymidine Thymidine kinase Thymidine Kinase - genetics Thymidine Kinase - metabolism Trametinib Transcription (Genetics) Transcription Factors - metabolism Tumors Xenograft Model Antitumor Assays |
| title | Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression |
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