B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by regulating HK2
Accumulating evidence suggests that aerobic glycolysis is important for colorectal cancer (CRC) development. However, the underlying mechanisms have yet to be elucidated. B7-H3, an immunoregulatory protein, is broadly overexpressed by multiple tumor types and plays a vital role in tumor progression....
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| Veröffentlicht in: | Cell death & disease 2019-04, Vol.10 (4), p.308-308, Article 308 |
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| creator | Shi, Tongguo Ma, Yanchao Cao, Lei Zhan, Shenghua Xu, Yunyun Fu, Fengqing Liu, Cuiping Zhang, Guangbo Wang, Zhenxin Wang, Ruoqin Lu, Huimin Lu, Binfeng Chen, Weichang Zhang, Xueguang |
| description | Accumulating evidence suggests that aerobic glycolysis is important for colorectal cancer (CRC) development. However, the underlying mechanisms have yet to be elucidated. B7-H3, an immunoregulatory protein, is broadly overexpressed by multiple tumor types and plays a vital role in tumor progression. In this study, we found that overexpression of B7-H3 effectively increased the rate of glucose consumption and lactate production, whereas knockdown of B7-H3 had the opposite effect. Furthermore, we showed that B7-H3 increased glucose consumption and lactate production by promoting hexokinase 2 (HK2) expression in CRC cells, and we also found that HK2 was a key mediator of B7-H3-induced CRC chemoresistance. Depletion of HK2 expression or treating cells with HK2 inhibitors could reverse the B7-H3-induced increase in aerobic glycolysis and B7-H3-endowed chemoresistance of cancer cells. Moreover, we verified a positive correlation between the expression of B7-H3 and HK2 in tumor tissues of CRC patients. Collectively, our findings suggest that B7-H3 may be a novel regulator of glucose metabolism and chemoresistance via controlling HK2 expression in CRC cells, a result that could help develop B7-H3 as a promising therapeutic target for CRC treatment. |
| doi_str_mv | 10.1038/s41419-019-1549-6 |
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However, the underlying mechanisms have yet to be elucidated. B7-H3, an immunoregulatory protein, is broadly overexpressed by multiple tumor types and plays a vital role in tumor progression. In this study, we found that overexpression of B7-H3 effectively increased the rate of glucose consumption and lactate production, whereas knockdown of B7-H3 had the opposite effect. Furthermore, we showed that B7-H3 increased glucose consumption and lactate production by promoting hexokinase 2 (HK2) expression in CRC cells, and we also found that HK2 was a key mediator of B7-H3-induced CRC chemoresistance. Depletion of HK2 expression or treating cells with HK2 inhibitors could reverse the B7-H3-induced increase in aerobic glycolysis and B7-H3-endowed chemoresistance of cancer cells. Moreover, we verified a positive correlation between the expression of B7-H3 and HK2 in tumor tissues of CRC patients. Collectively, our findings suggest that B7-H3 may be a novel regulator of glucose metabolism and chemoresistance via controlling HK2 expression in CRC cells, a result that could help develop B7-H3 as a promising therapeutic target for CRC treatment.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-019-1549-6</identifier><identifier>PMID: 30952834</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 13/89 ; 13/95 ; 631/67/1504/1885 ; 631/67/2327 ; 631/80/304 ; 64/60 ; Animals ; Antibodies ; Apoptosis - drug effects ; Apoptosis - genetics ; B7 antigen ; B7 Antigens - genetics ; B7 Antigens - metabolism ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Cell Proliferation - drug effects ; Cell Proliferation - genetics ; Chemoresistance ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Drug Resistance, Neoplasm - drug effects ; Drug Resistance, Neoplasm - genetics ; Female ; Glucose ; Glucose - metabolism ; Glycolysis ; Glycolysis - genetics ; Glycolysis - physiology ; HCT116 Cells ; Hexokinase ; Hexokinase - genetics ; Hexokinase - metabolism ; Humans ; Immunology ; Immunoregulation ; Lactic acid ; Lactic Acid - biosynthesis ; Lactic Acid - metabolism ; Life Sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; Therapeutic applications ; Transplantation, Heterologous ; Up-Regulation</subject><ispartof>Cell death & disease, 2019-04, Vol.10 (4), p.308-308, Article 308</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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><citedby>FETCH-LOGICAL-c470t-8d53124d33cb750879e3aa5ec424cd92117afec7cbdee8ff12d3c109cb8105aa3</citedby><cites>FETCH-LOGICAL-c470t-8d53124d33cb750879e3aa5ec424cd92117afec7cbdee8ff12d3c109cb8105aa3</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/PMC6450969/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450969/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30952834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Tongguo</creatorcontrib><creatorcontrib>Ma, Yanchao</creatorcontrib><creatorcontrib>Cao, Lei</creatorcontrib><creatorcontrib>Zhan, Shenghua</creatorcontrib><creatorcontrib>Xu, Yunyun</creatorcontrib><creatorcontrib>Fu, Fengqing</creatorcontrib><creatorcontrib>Liu, Cuiping</creatorcontrib><creatorcontrib>Zhang, Guangbo</creatorcontrib><creatorcontrib>Wang, Zhenxin</creatorcontrib><creatorcontrib>Wang, Ruoqin</creatorcontrib><creatorcontrib>Lu, Huimin</creatorcontrib><creatorcontrib>Lu, Binfeng</creatorcontrib><creatorcontrib>Chen, Weichang</creatorcontrib><creatorcontrib>Zhang, Xueguang</creatorcontrib><title>B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by regulating HK2</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Accumulating evidence suggests that aerobic glycolysis is important for colorectal cancer (CRC) development. However, the underlying mechanisms have yet to be elucidated. B7-H3, an immunoregulatory protein, is broadly overexpressed by multiple tumor types and plays a vital role in tumor progression. In this study, we found that overexpression of B7-H3 effectively increased the rate of glucose consumption and lactate production, whereas knockdown of B7-H3 had the opposite effect. Furthermore, we showed that B7-H3 increased glucose consumption and lactate production by promoting hexokinase 2 (HK2) expression in CRC cells, and we also found that HK2 was a key mediator of B7-H3-induced CRC chemoresistance. Depletion of HK2 expression or treating cells with HK2 inhibitors could reverse the B7-H3-induced increase in aerobic glycolysis and B7-H3-endowed chemoresistance of cancer cells. Moreover, we verified a positive correlation between the expression of B7-H3 and HK2 in tumor tissues of CRC patients. Collectively, our findings suggest that B7-H3 may be a novel regulator of glucose metabolism and chemoresistance via controlling HK2 expression in CRC cells, a result that could help develop B7-H3 as a promising therapeutic target for CRC treatment.</description><subject>13/51</subject><subject>13/89</subject><subject>13/95</subject><subject>631/67/1504/1885</subject><subject>631/67/2327</subject><subject>631/80/304</subject><subject>64/60</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>B7 antigen</subject><subject>B7 Antigens - genetics</subject><subject>B7 Antigens - metabolism</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - genetics</subject><subject>Chemoresistance</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - 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metabolism</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunoregulation</topic><topic>Lactic acid</topic><topic>Lactic Acid - biosynthesis</topic><topic>Lactic Acid - metabolism</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>STAT3 Transcription Factor - genetics</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Therapeutic applications</topic><topic>Transplantation, Heterologous</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Tongguo</creatorcontrib><creatorcontrib>Ma, Yanchao</creatorcontrib><creatorcontrib>Cao, Lei</creatorcontrib><creatorcontrib>Zhan, Shenghua</creatorcontrib><creatorcontrib>Xu, Yunyun</creatorcontrib><creatorcontrib>Fu, Fengqing</creatorcontrib><creatorcontrib>Liu, Cuiping</creatorcontrib><creatorcontrib>Zhang, Guangbo</creatorcontrib><creatorcontrib>Wang, Zhenxin</creatorcontrib><creatorcontrib>Wang, Ruoqin</creatorcontrib><creatorcontrib>Lu, Huimin</creatorcontrib><creatorcontrib>Lu, Binfeng</creatorcontrib><creatorcontrib>Chen, Weichang</creatorcontrib><creatorcontrib>Zhang, Xueguang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Science Database</collection><collection>Biological Science Database</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>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Tongguo</au><au>Ma, Yanchao</au><au>Cao, Lei</au><au>Zhan, Shenghua</au><au>Xu, Yunyun</au><au>Fu, Fengqing</au><au>Liu, Cuiping</au><au>Zhang, Guangbo</au><au>Wang, Zhenxin</au><au>Wang, Ruoqin</au><au>Lu, Huimin</au><au>Lu, Binfeng</au><au>Chen, Weichang</au><au>Zhang, Xueguang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by regulating HK2</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-04-05</date><risdate>2019</risdate><volume>10</volume><issue>4</issue><spage>308</spage><epage>308</epage><pages>308-308</pages><artnum>308</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Accumulating evidence suggests that aerobic glycolysis is important for colorectal cancer (CRC) development. However, the underlying mechanisms have yet to be elucidated. B7-H3, an immunoregulatory protein, is broadly overexpressed by multiple tumor types and plays a vital role in tumor progression. In this study, we found that overexpression of B7-H3 effectively increased the rate of glucose consumption and lactate production, whereas knockdown of B7-H3 had the opposite effect. Furthermore, we showed that B7-H3 increased glucose consumption and lactate production by promoting hexokinase 2 (HK2) expression in CRC cells, and we also found that HK2 was a key mediator of B7-H3-induced CRC chemoresistance. Depletion of HK2 expression or treating cells with HK2 inhibitors could reverse the B7-H3-induced increase in aerobic glycolysis and B7-H3-endowed chemoresistance of cancer cells. Moreover, we verified a positive correlation between the expression of B7-H3 and HK2 in tumor tissues of CRC patients. Collectively, our findings suggest that B7-H3 may be a novel regulator of glucose metabolism and chemoresistance via controlling HK2 expression in CRC cells, a result that could help develop B7-H3 as a promising therapeutic target for CRC treatment.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30952834</pmid><doi>10.1038/s41419-019-1549-6</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/51 13/89 13/95 631/67/1504/1885 631/67/2327 631/80/304 64/60 Animals Antibodies Apoptosis - drug effects Apoptosis - genetics B7 antigen B7 Antigens - genetics B7 Antigens - metabolism Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell Proliferation - drug effects Cell Proliferation - genetics Chemoresistance Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Female Glucose Glucose - metabolism Glycolysis Glycolysis - genetics Glycolysis - physiology HCT116 Cells Hexokinase Hexokinase - genetics Hexokinase - metabolism Humans Immunology Immunoregulation Lactic acid Lactic Acid - biosynthesis Lactic Acid - metabolism Life Sciences Mice Mice, Inbred BALB C Mice, Nude STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism Therapeutic applications Transplantation, Heterologous Up-Regulation |
| title | B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by regulating HK2 |
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