Monocarboxylate transporter dependent mechanism is involved in proliferation, migration, and invasion of human glioblastoma cell lines via activation of PI3K/Akt signaling pathway
Glioblastoma multiforme is one of the most common primary tumors of the central nervous system, with a very poor prognosis. Cancer cells have been observed to upregulate pH regulators, such as monocarboxylate transporters (MCTs), with an increase in MCT4 expression being observed in several malignan...
Gespeichert in:
Veröffentlicht in: | PloS one 2024-10, Vol.19 (10), p.e0312939 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 10 |
container_start_page | e0312939 |
container_title | PloS one |
container_volume | 19 |
creator | Gao, Chen Yang, Binni Li, Yurong Pei, Wenjuan |
description | Glioblastoma multiforme is one of the most common primary tumors of the central nervous system, with a very poor prognosis. Cancer cells have been observed to upregulate pH regulators, such as monocarboxylate transporters (MCTs), with an increase in MCT4 expression being observed in several malignancies. MCT4/ recombinant cluster of differentiation 147 (CD147) transporter complex was reported to stimulate vascular endothelial growth factor (VEGF) via the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (Akt) pathway, which has been proven to mediate glioblastoma invasion and migration. The present study aimed to clarify the role of the MCT4/CD147 transporter complex in glioblastoma cell proliferation, migration, and invasion. In this work, lentiviral vectors were used to overexpress MCT4/CD147 and small interfering RNA (siRNA) was used to silence MCT4/CD147 in the human glioma cell lines U87 and U251, respectively. The effects on cell proliferation, migration and invasiveness, as well as the protein expression levels of MCT4 and CD147, extracellular lactate content and Akt activation were assessed by MTT, wound-healing and invasion assays, western blotting and colorimetric method, respectively. The analysis results suggested that cell proliferation, migration, invasion, and Akt activation were decreased by siRNA in all cell lines, but were increased by lentivirus-mediated MCT4 overexpression. These findings suggest that inhibiting the activity and expression of the MCT4/CD147 transporter complex via metabolic-targeting drugs, particularly in cells with a high rate of glycolysis, should be explored as a novel strategy for glioblastoma treatment. |
doi_str_mv | 10.1371/journal.pone.0312939 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_3122530302</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A814242077</galeid><doaj_id>oai_doaj_org_article_5eb0ecd25d61416092fe56a9cf015a3d</doaj_id><sourcerecordid>A814242077</sourcerecordid><originalsourceid>FETCH-LOGICAL-c572t-572d420497a3319f0473d33c7d7ba2beea446903da034feb8651b03871aa6cb33</originalsourceid><addsrcrecordid>eNqNk9tu1DAQhiMEoqXwBggsVUIgsVs7zmFzhaqKw4qiIk631sSZZF0cO9jO0j4XL4jT3VZd1AsUKZnY3z_2_PYkyVNG54yX7Ojcjs6Ang_W4Jxylla8upfss4qnsyKl_P6teC955P05pTlfFMXDZI9XWZlXNN9P_nyyxkpwtb241BCQBAfGD9YFdKTBAU2DJpAe5QqM8j1RniiztnqNTQzI4KxWLToIyprXpFfddQhmAtbg4x-xLVmNPRjSaWVrDT7YHohErYlWBj1ZKyAgg1pfqSf-85J_PDr-GYhXXaxTmY4MEFa_4fJx8qAF7fHJ9nuQfH_39tvJh9np2fvlyfHpTOZlGmbx1WQpzaoSOGdVS7OSN5zLsilrSGtEyLKiorwByrMW60WRs5ryRckACllzfpA83-QdtPVi67cX0eo055TTNBLLDdFYOBeDUz24S2FBiasB6zoBLiipUeRYU5RNmjcFy1hBq7TFvIBKtpTlEDd2kLzZrjbWPTYy2u5A7yTdnTFqJTq7FozlaZbTRczwcpvB2V8j-iB65SePwaAdNxsveFZkE3r4D3p3eVuqg1iBMq2NC8spqThesCyN7pZlpOZ3UPFpsFcy3s5WxfEdwasdQWQCXoQORu_F8uuX_2fPfuyyL26xKwQdVt7qcbpRfhfMNqB01nuH7Y3LjIqpua7dEFNziW1zRdmz2yd0I7ruJv4XXN0idg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3122530302</pqid></control><display><type>article</type><title>Monocarboxylate transporter dependent mechanism is involved in proliferation, migration, and invasion of human glioblastoma cell lines via activation of PI3K/Akt signaling pathway</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Gao, Chen ; Yang, Binni ; Li, Yurong ; Pei, Wenjuan</creator><contributor>Amodio, Nicola</contributor><creatorcontrib>Gao, Chen ; Yang, Binni ; Li, Yurong ; Pei, Wenjuan ; Amodio, Nicola</creatorcontrib><description>Glioblastoma multiforme is one of the most common primary tumors of the central nervous system, with a very poor prognosis. Cancer cells have been observed to upregulate pH regulators, such as monocarboxylate transporters (MCTs), with an increase in MCT4 expression being observed in several malignancies. MCT4/ recombinant cluster of differentiation 147 (CD147) transporter complex was reported to stimulate vascular endothelial growth factor (VEGF) via the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (Akt) pathway, which has been proven to mediate glioblastoma invasion and migration. The present study aimed to clarify the role of the MCT4/CD147 transporter complex in glioblastoma cell proliferation, migration, and invasion. In this work, lentiviral vectors were used to overexpress MCT4/CD147 and small interfering RNA (siRNA) was used to silence MCT4/CD147 in the human glioma cell lines U87 and U251, respectively. The effects on cell proliferation, migration and invasiveness, as well as the protein expression levels of MCT4 and CD147, extracellular lactate content and Akt activation were assessed by MTT, wound-healing and invasion assays, western blotting and colorimetric method, respectively. The analysis results suggested that cell proliferation, migration, invasion, and Akt activation were decreased by siRNA in all cell lines, but were increased by lentivirus-mediated MCT4 overexpression. These findings suggest that inhibiting the activity and expression of the MCT4/CD147 transporter complex via metabolic-targeting drugs, particularly in cells with a high rate of glycolysis, should be explored as a novel strategy for glioblastoma treatment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0312939</identifier><identifier>PMID: 39475905</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Analysis ; Antibodies ; Basigin - genetics ; Basigin - metabolism ; Biology and life sciences ; Brain tumors ; Care and treatment ; Carrier proteins ; CD147 antigen ; Cell activation ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Cell Proliferation ; Central nervous system ; Colorimetry ; Development and progression ; Drug delivery ; Gene expression ; Glioblastoma ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Glioblastoma multiforme ; Glioma ; Glioma cells ; Glycolysis ; Growth factors ; Health aspects ; Humans ; Invasiveness ; Kinases ; Malignancy ; Medicine and Health Sciences ; Metabolism ; Monocarboxylic Acid Transporters - genetics ; Monocarboxylic Acid Transporters - metabolism ; Muscle Proteins - genetics ; Muscle Proteins - metabolism ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases - metabolism ; Prognosis ; Protein kinases ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Research and Analysis Methods ; Risk factors ; RNA ; Signal Transduction ; siRNA ; Variance analysis ; Vascular endothelial growth factor ; Western blotting ; Wound healing</subject><ispartof>PloS one, 2024-10, Vol.19 (10), p.e0312939</ispartof><rights>Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Gao 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>2024 Gao et al 2024 Gao et al</rights><rights>2024 Gao 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c572t-572d420497a3319f0473d33c7d7ba2beea446903da034feb8651b03871aa6cb33</cites><orcidid>0000-0002-4699-099X</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/PMC11524508/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524508/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39475905$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Amodio, Nicola</contributor><creatorcontrib>Gao, Chen</creatorcontrib><creatorcontrib>Yang, Binni</creatorcontrib><creatorcontrib>Li, Yurong</creatorcontrib><creatorcontrib>Pei, Wenjuan</creatorcontrib><title>Monocarboxylate transporter dependent mechanism is involved in proliferation, migration, and invasion of human glioblastoma cell lines via activation of PI3K/Akt signaling pathway</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Glioblastoma multiforme is one of the most common primary tumors of the central nervous system, with a very poor prognosis. Cancer cells have been observed to upregulate pH regulators, such as monocarboxylate transporters (MCTs), with an increase in MCT4 expression being observed in several malignancies. MCT4/ recombinant cluster of differentiation 147 (CD147) transporter complex was reported to stimulate vascular endothelial growth factor (VEGF) via the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (Akt) pathway, which has been proven to mediate glioblastoma invasion and migration. The present study aimed to clarify the role of the MCT4/CD147 transporter complex in glioblastoma cell proliferation, migration, and invasion. In this work, lentiviral vectors were used to overexpress MCT4/CD147 and small interfering RNA (siRNA) was used to silence MCT4/CD147 in the human glioma cell lines U87 and U251, respectively. The effects on cell proliferation, migration and invasiveness, as well as the protein expression levels of MCT4 and CD147, extracellular lactate content and Akt activation were assessed by MTT, wound-healing and invasion assays, western blotting and colorimetric method, respectively. The analysis results suggested that cell proliferation, migration, invasion, and Akt activation were decreased by siRNA in all cell lines, but were increased by lentivirus-mediated MCT4 overexpression. These findings suggest that inhibiting the activity and expression of the MCT4/CD147 transporter complex via metabolic-targeting drugs, particularly in cells with a high rate of glycolysis, should be explored as a novel strategy for glioblastoma treatment.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Antibodies</subject><subject>Basigin - genetics</subject><subject>Basigin - metabolism</subject><subject>Biology and life sciences</subject><subject>Brain tumors</subject><subject>Care and treatment</subject><subject>Carrier proteins</subject><subject>CD147 antigen</subject><subject>Cell activation</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Central nervous system</subject><subject>Colorimetry</subject><subject>Development and progression</subject><subject>Drug delivery</subject><subject>Gene expression</subject><subject>Glioblastoma</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma multiforme</subject><subject>Glioma</subject><subject>Glioma cells</subject><subject>Glycolysis</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Kinases</subject><subject>Malignancy</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Monocarboxylic Acid Transporters - genetics</subject><subject>Monocarboxylic Acid Transporters - metabolism</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - metabolism</subject><subject>Neoplasm Invasiveness</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Prognosis</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Research and Analysis Methods</subject><subject>Risk factors</subject><subject>RNA</subject><subject>Signal Transduction</subject><subject>siRNA</subject><subject>Variance analysis</subject><subject>Vascular endothelial growth factor</subject><subject>Western blotting</subject><subject>Wound healing</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</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>eNqNk9tu1DAQhiMEoqXwBggsVUIgsVs7zmFzhaqKw4qiIk631sSZZF0cO9jO0j4XL4jT3VZd1AsUKZnY3z_2_PYkyVNG54yX7Ojcjs6Ang_W4Jxylla8upfss4qnsyKl_P6teC955P05pTlfFMXDZI9XWZlXNN9P_nyyxkpwtb241BCQBAfGD9YFdKTBAU2DJpAe5QqM8j1RniiztnqNTQzI4KxWLToIyprXpFfddQhmAtbg4x-xLVmNPRjSaWVrDT7YHohErYlWBj1ZKyAgg1pfqSf-85J_PDr-GYhXXaxTmY4MEFa_4fJx8qAF7fHJ9nuQfH_39tvJh9np2fvlyfHpTOZlGmbx1WQpzaoSOGdVS7OSN5zLsilrSGtEyLKiorwByrMW60WRs5ryRckACllzfpA83-QdtPVi67cX0eo055TTNBLLDdFYOBeDUz24S2FBiasB6zoBLiipUeRYU5RNmjcFy1hBq7TFvIBKtpTlEDd2kLzZrjbWPTYy2u5A7yTdnTFqJTq7FozlaZbTRczwcpvB2V8j-iB65SePwaAdNxsveFZkE3r4D3p3eVuqg1iBMq2NC8spqThesCyN7pZlpOZ3UPFpsFcy3s5WxfEdwasdQWQCXoQORu_F8uuX_2fPfuyyL26xKwQdVt7qcbpRfhfMNqB01nuH7Y3LjIqpua7dEFNziW1zRdmz2yd0I7ruJv4XXN0idg</recordid><startdate>20241030</startdate><enddate>20241030</enddate><creator>Gao, Chen</creator><creator>Yang, Binni</creator><creator>Li, Yurong</creator><creator>Pei, Wenjuan</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4699-099X</orcidid></search><sort><creationdate>20241030</creationdate><title>Monocarboxylate transporter dependent mechanism is involved in proliferation, migration, and invasion of human glioblastoma cell lines via activation of PI3K/Akt signaling pathway</title><author>Gao, Chen ; Yang, Binni ; Li, Yurong ; Pei, Wenjuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-572d420497a3319f0473d33c7d7ba2beea446903da034feb8651b03871aa6cb33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Analysis</topic><topic>Antibodies</topic><topic>Basigin - genetics</topic><topic>Basigin - metabolism</topic><topic>Biology and life sciences</topic><topic>Brain tumors</topic><topic>Care and treatment</topic><topic>Carrier proteins</topic><topic>CD147 antigen</topic><topic>Cell activation</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Central nervous system</topic><topic>Colorimetry</topic><topic>Development and progression</topic><topic>Drug delivery</topic><topic>Gene expression</topic><topic>Glioblastoma</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - metabolism</topic><topic>Glioblastoma - pathology</topic><topic>Glioblastoma multiforme</topic><topic>Glioma</topic><topic>Glioma cells</topic><topic>Glycolysis</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Kinases</topic><topic>Malignancy</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Monocarboxylic Acid Transporters - genetics</topic><topic>Monocarboxylic Acid Transporters - metabolism</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle Proteins - metabolism</topic><topic>Neoplasm Invasiveness</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Prognosis</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Research and Analysis Methods</topic><topic>Risk factors</topic><topic>RNA</topic><topic>Signal Transduction</topic><topic>siRNA</topic><topic>Variance analysis</topic><topic>Vascular endothelial growth factor</topic><topic>Western blotting</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gao, Chen</creatorcontrib><creatorcontrib>Yang, Binni</creatorcontrib><creatorcontrib>Li, Yurong</creatorcontrib><creatorcontrib>Pei, Wenjuan</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: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</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 one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gao, Chen</au><au>Yang, Binni</au><au>Li, Yurong</au><au>Pei, Wenjuan</au><au>Amodio, Nicola</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monocarboxylate transporter dependent mechanism is involved in proliferation, migration, and invasion of human glioblastoma cell lines via activation of PI3K/Akt signaling pathway</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-10-30</date><risdate>2024</risdate><volume>19</volume><issue>10</issue><spage>e0312939</spage><pages>e0312939-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Glioblastoma multiforme is one of the most common primary tumors of the central nervous system, with a very poor prognosis. Cancer cells have been observed to upregulate pH regulators, such as monocarboxylate transporters (MCTs), with an increase in MCT4 expression being observed in several malignancies. MCT4/ recombinant cluster of differentiation 147 (CD147) transporter complex was reported to stimulate vascular endothelial growth factor (VEGF) via the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (Akt) pathway, which has been proven to mediate glioblastoma invasion and migration. The present study aimed to clarify the role of the MCT4/CD147 transporter complex in glioblastoma cell proliferation, migration, and invasion. In this work, lentiviral vectors were used to overexpress MCT4/CD147 and small interfering RNA (siRNA) was used to silence MCT4/CD147 in the human glioma cell lines U87 and U251, respectively. The effects on cell proliferation, migration and invasiveness, as well as the protein expression levels of MCT4 and CD147, extracellular lactate content and Akt activation were assessed by MTT, wound-healing and invasion assays, western blotting and colorimetric method, respectively. The analysis results suggested that cell proliferation, migration, invasion, and Akt activation were decreased by siRNA in all cell lines, but were increased by lentivirus-mediated MCT4 overexpression. These findings suggest that inhibiting the activity and expression of the MCT4/CD147 transporter complex via metabolic-targeting drugs, particularly in cells with a high rate of glycolysis, should be explored as a novel strategy for glioblastoma treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39475905</pmid><doi>10.1371/journal.pone.0312939</doi><tpages>e0312939</tpages><orcidid>https://orcid.org/0000-0002-4699-099X</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2024-10, Vol.19 (10), p.e0312939 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_3122530302 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | 1-Phosphatidylinositol 3-kinase AKT protein Analysis Antibodies Basigin - genetics Basigin - metabolism Biology and life sciences Brain tumors Care and treatment Carrier proteins CD147 antigen Cell activation Cell Line, Tumor Cell migration Cell Movement Cell Proliferation Central nervous system Colorimetry Development and progression Drug delivery Gene expression Glioblastoma Glioblastoma - genetics Glioblastoma - metabolism Glioblastoma - pathology Glioblastoma multiforme Glioma Glioma cells Glycolysis Growth factors Health aspects Humans Invasiveness Kinases Malignancy Medicine and Health Sciences Metabolism Monocarboxylic Acid Transporters - genetics Monocarboxylic Acid Transporters - metabolism Muscle Proteins - genetics Muscle Proteins - metabolism Neoplasm Invasiveness Phosphatidylinositol 3-Kinases - metabolism Prognosis Protein kinases Proteins Proto-Oncogene Proteins c-akt - metabolism Research and Analysis Methods Risk factors RNA Signal Transduction siRNA Variance analysis Vascular endothelial growth factor Western blotting Wound healing |
title | Monocarboxylate transporter dependent mechanism is involved in proliferation, migration, and invasion of human glioblastoma cell lines via activation of PI3K/Akt signaling pathway |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T13%3A50%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Monocarboxylate%20transporter%20dependent%20mechanism%20is%20involved%20in%20proliferation,%20migration,%20and%20invasion%20of%20human%20glioblastoma%20cell%20lines%20via%20activation%20of%20PI3K/Akt%20signaling%20pathway&rft.jtitle=PloS%20one&rft.au=Gao,%20Chen&rft.date=2024-10-30&rft.volume=19&rft.issue=10&rft.spage=e0312939&rft.pages=e0312939-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0312939&rft_dat=%3Cgale_plos_%3EA814242077%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3122530302&rft_id=info:pmid/39475905&rft_galeid=A814242077&rft_doaj_id=oai_doaj_org_article_5eb0ecd25d61416092fe56a9cf015a3d&rfr_iscdi=true |