CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming
Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a...
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| Veröffentlicht in: | Oncotarget 2017-01, Vol.8 (4), p.6742-6762 |
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| creator | Kendrick, Agnieszka A Schafer, Johnathon Dzieciatkowska, Monika Nemkov, Travis D'Alessandro, Angelo Neelakantan, Deepika Ford, Heide L Pearson, Chad G Weekes, Colin D Hansen, Kirk C Eisenmesser, Elan Z |
| description | Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner's proteasome-dependent degradation and incorrect plasma membrane localization through the CD147 transmembrane (TM) region. The interactions with transmembrane small molecule and ion transporters identified here indicate a central role of CD147 in pancreatic cancer metabolic reprogramming, particularly with respect to amino acid anabolism and calcium signaling. Importantly, CD147 genetic ablation prevents pancreatic cancer cell proliferation and tumor growth in vitro and in vivo in conjunction with metabolic rewiring towards amino acid anabolism, thus paving the way for future combined pharmacological treatments. |
| doi_str_mv | 10.18632/oncotarget.14272 |
| format | Article |
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Importantly, CD147 genetic ablation prevents pancreatic cancer cell proliferation and tumor growth in vitro and in vivo in conjunction with metabolic rewiring towards amino acid anabolism, thus paving the way for future combined pharmacological treatments.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.14272</identifier><identifier>PMID: 28039486</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Amino Acids - metabolism ; Animals ; Basigin - genetics ; Basigin - metabolism ; Calcium Signaling ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cellular Reprogramming ; Energy Metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Transport Proteins - genetics ; Membrane Transport Proteins - metabolism ; Mice, Nude ; Monocarboxylic Acid Transporters - genetics ; Monocarboxylic Acid Transporters - metabolism ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Plasma Membrane Calcium-Transporting ATPases - genetics ; Plasma Membrane Calcium-Transporting ATPases - metabolism ; Proteasome Endopeptidase Complex - metabolism ; Protein Binding ; Proteolysis ; Research Paper ; RNA Interference ; Time Factors ; Transfection ; Tumor Burden</subject><ispartof>Oncotarget, 2017-01, Vol.8 (4), p.6742-6762</ispartof><rights>Copyright: © 2017 Kendrick et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-a7dbc55d7fcc23eb54527ea113895e14fa3e475082b407f2fc45aaaedb6ef5993</citedby><cites>FETCH-LOGICAL-c422t-a7dbc55d7fcc23eb54527ea113895e14fa3e475082b407f2fc45aaaedb6ef5993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341751/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341751/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,887,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28039486$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kendrick, Agnieszka A</creatorcontrib><creatorcontrib>Schafer, Johnathon</creatorcontrib><creatorcontrib>Dzieciatkowska, Monika</creatorcontrib><creatorcontrib>Nemkov, Travis</creatorcontrib><creatorcontrib>D'Alessandro, Angelo</creatorcontrib><creatorcontrib>Neelakantan, Deepika</creatorcontrib><creatorcontrib>Ford, Heide L</creatorcontrib><creatorcontrib>Pearson, Chad G</creatorcontrib><creatorcontrib>Weekes, Colin D</creatorcontrib><creatorcontrib>Hansen, Kirk C</creatorcontrib><creatorcontrib>Eisenmesser, Elan Z</creatorcontrib><title>CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). 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Importantly, CD147 genetic ablation prevents pancreatic cancer cell proliferation and tumor growth in vitro and in vivo in conjunction with metabolic rewiring towards amino acid anabolism, thus paving the way for future combined pharmacological treatments.</description><subject>Amino Acids - metabolism</subject><subject>Animals</subject><subject>Basigin - genetics</subject><subject>Basigin - metabolism</subject><subject>Calcium Signaling</subject><subject>Cell Adhesion</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cellular Reprogramming</subject><subject>Energy Metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Mice, Nude</subject><subject>Monocarboxylic Acid Transporters - genetics</subject><subject>Monocarboxylic Acid Transporters - metabolism</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Plasma Membrane Calcium-Transporting ATPases - genetics</subject><subject>Plasma Membrane Calcium-Transporting ATPases - metabolism</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Protein Binding</subject><subject>Proteolysis</subject><subject>Research Paper</subject><subject>RNA Interference</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Tumor Burden</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1v1DAQhi0EolXpD-BS-chl2_hrnfSAhBZokSpxgbM1cSa7BjtObadSr_3lmN22lLl4ZM_7zHheQt6z5py1a8Ev4mRjgbTFcs4k1_wVOWad7FZcKfH6RX5ETnP-1dRQUre8e0uOeNuITrbrY_Kw-cykvqRAcwDvaYge7eKRlgRTnmMqmChM1nkP6Z7OKRZ0E4VCyw6pTTHnFGGgcaRh8cXNVbqroADpd_57a6t4jxhowAJ99M7ShBW0TRCCm7bvyJsRfMbTx_OE_Pz65cfmenXz_erb5tPNykrOywr00FulBj1aywX2SiquERgTbaeQyREESq2alvey0SMfrVQAgEO_xlF1nTghHw_ceekDDhan-kdv5uTqsPcmgjP_v0xuZ7bxzighmVasAj48AlK8XTAXE1y2WDczYVyyYa2Sa8a1FrWUHUoPG8LxuQ1rzN4-888-s7evas5ezveseDJL_AHVXp00</recordid><startdate>20170124</startdate><enddate>20170124</enddate><creator>Kendrick, Agnieszka A</creator><creator>Schafer, Johnathon</creator><creator>Dzieciatkowska, Monika</creator><creator>Nemkov, Travis</creator><creator>D'Alessandro, Angelo</creator><creator>Neelakantan, Deepika</creator><creator>Ford, Heide L</creator><creator>Pearson, Chad G</creator><creator>Weekes, Colin D</creator><creator>Hansen, Kirk C</creator><creator>Eisenmesser, Elan Z</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170124</creationdate><title>CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming</title><author>Kendrick, Agnieszka A ; Schafer, Johnathon ; Dzieciatkowska, Monika ; Nemkov, Travis ; D'Alessandro, Angelo ; Neelakantan, Deepika ; Ford, Heide L ; Pearson, Chad G ; Weekes, Colin D ; Hansen, Kirk C ; Eisenmesser, Elan Z</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-a7dbc55d7fcc23eb54527ea113895e14fa3e475082b407f2fc45aaaedb6ef5993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amino Acids - metabolism</topic><topic>Animals</topic><topic>Basigin - genetics</topic><topic>Basigin - metabolism</topic><topic>Calcium Signaling</topic><topic>Cell Adhesion</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cellular Reprogramming</topic><topic>Energy Metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Membrane Transport Proteins - genetics</topic><topic>Membrane Transport Proteins - metabolism</topic><topic>Mice, Nude</topic><topic>Monocarboxylic Acid Transporters - genetics</topic><topic>Monocarboxylic Acid Transporters - metabolism</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Plasma Membrane Calcium-Transporting ATPases - genetics</topic><topic>Plasma Membrane Calcium-Transporting ATPases - metabolism</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Protein Binding</topic><topic>Proteolysis</topic><topic>Research Paper</topic><topic>RNA Interference</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Tumor Burden</topic><toplevel>online_resources</toplevel><creatorcontrib>Kendrick, Agnieszka A</creatorcontrib><creatorcontrib>Schafer, Johnathon</creatorcontrib><creatorcontrib>Dzieciatkowska, Monika</creatorcontrib><creatorcontrib>Nemkov, Travis</creatorcontrib><creatorcontrib>D'Alessandro, Angelo</creatorcontrib><creatorcontrib>Neelakantan, Deepika</creatorcontrib><creatorcontrib>Ford, Heide L</creatorcontrib><creatorcontrib>Pearson, Chad G</creatorcontrib><creatorcontrib>Weekes, Colin D</creatorcontrib><creatorcontrib>Hansen, Kirk C</creatorcontrib><creatorcontrib>Eisenmesser, Elan Z</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kendrick, Agnieszka A</au><au>Schafer, Johnathon</au><au>Dzieciatkowska, Monika</au><au>Nemkov, Travis</au><au>D'Alessandro, Angelo</au><au>Neelakantan, Deepika</au><au>Ford, Heide L</au><au>Pearson, Chad G</au><au>Weekes, Colin D</au><au>Hansen, Kirk C</au><au>Eisenmesser, Elan Z</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-01-24</date><risdate>2017</risdate><volume>8</volume><issue>4</issue><spage>6742</spage><epage>6762</epage><pages>6742-6762</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). 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| source | MEDLINE; PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free E- Journals |
| subjects | Amino Acids - metabolism Animals Basigin - genetics Basigin - metabolism Calcium Signaling Cell Adhesion Cell Line, Tumor Cell Movement Cell Proliferation Cellular Reprogramming Energy Metabolism Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism Mice, Nude Monocarboxylic Acid Transporters - genetics Monocarboxylic Acid Transporters - metabolism Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Plasma Membrane Calcium-Transporting ATPases - genetics Plasma Membrane Calcium-Transporting ATPases - metabolism Proteasome Endopeptidase Complex - metabolism Protein Binding Proteolysis Research Paper RNA Interference Time Factors Transfection Tumor Burden |
| title | CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming |
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