Hypoxia‐inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression
Lung cancer treatment is difficult owing to chemoresistance. Hypoxia‐inducible factor 1 (HIF‐1) and HIF‐1‐induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF‐1α and carbonic anhydrase IX (CAIX), a transmembrane protei...
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| Veröffentlicht in: | Cancer medicine (Malden, MA) MA), 2017-01, Vol.6 (1), p.288-297 |
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| creator | Sowa, Terumasa Menju, Toshi Chen‐Yoshikawa, Toyofumi F. Takahashi, Koji Nishikawa, Shigeto Nakanishi, Takao Shikuma, Kei Motoyama, Hideki Hijiya, Kyoko Aoyama, Akihiro Sato, Toshihiko Sonobe, Makoto Harada, Hiroshi Date, Hiroshi |
| description | Lung cancer treatment is difficult owing to chemoresistance. Hypoxia‐inducible factor 1 (HIF‐1) and HIF‐1‐induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF‐1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF‐1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF‐1α‐induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF‐1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF‐1α, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF‐1α expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF‐1‐dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF‐1α in A549 cells. HIF‐1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF‐1α, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF‐1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.
Hypoxia‐inducible factor 1 (HIF‐1) and carbonic anhydrase IX (CAIX) affected the chemosensitivity of lung cancer cell line and prognosis of lung cancer patients after induction chemoradiotherapy. Inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients. |
| doi_str_mv | 10.1002/cam4.991 |
| format | Article |
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Hypoxia‐inducible factor 1 (HIF‐1) and carbonic anhydrase IX (CAIX) affected the chemosensitivity of lung cancer cell line and prognosis of lung cancer patients after induction chemoradiotherapy. Inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients.</description><identifier>ISSN: 2045-7634</identifier><identifier>EISSN: 2045-7634</identifier><identifier>DOI: 10.1002/cam4.991</identifier><identifier>PMID: 28028936</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>A549 Cells ; Acidosis ; Aged ; Antigens, Neoplasm - metabolism ; Cancer Biology ; Cancer therapies ; Carbonic anhydrase IX ; Carbonic Anhydrase IX - metabolism ; Carbonic anhydrases ; Cell growth ; Cell Hypoxia ; Chemoradiotherapy ; Chemoresistance ; Chemotherapy ; Cytotoxicity ; Drug Resistance, Neoplasm ; Experiments ; Female ; Glucose transporter ; Glucose Transporter Type 1 - metabolism ; Glycolysis ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; hypoxia‐inducible factor 1 ; induction chemoradiotherapy ; Lung cancer ; Lung Neoplasms - metabolism ; Lung Neoplasms - therapy ; Lymphatic system ; Male ; Manufacturers ; Metabolic pathways ; Metastasis ; Middle Aged ; Mutation ; Original Research ; Oxidative phosphorylation ; Patients ; Phosphorylation ; Plasmids ; Prognosis ; Studies ; Vinblastine - analogs & derivatives ; Vinblastine - pharmacology ; Vinblastine - therapeutic use ; Vinorelbine</subject><ispartof>Cancer medicine (Malden, MA), 2017-01, Vol.6 (1), p.288-297</ispartof><rights>2016 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.</rights><rights>2017. 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-c5481-bb34c104ea04729cbd970af3b969db8895c26f835d69678dd1a6be503d3b63723</citedby><cites>FETCH-LOGICAL-c5481-bb34c104ea04729cbd970af3b969db8895c26f835d69678dd1a6be503d3b63723</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/PMC5269694/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269694/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28028936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sowa, Terumasa</creatorcontrib><creatorcontrib>Menju, Toshi</creatorcontrib><creatorcontrib>Chen‐Yoshikawa, Toyofumi F.</creatorcontrib><creatorcontrib>Takahashi, Koji</creatorcontrib><creatorcontrib>Nishikawa, Shigeto</creatorcontrib><creatorcontrib>Nakanishi, Takao</creatorcontrib><creatorcontrib>Shikuma, Kei</creatorcontrib><creatorcontrib>Motoyama, Hideki</creatorcontrib><creatorcontrib>Hijiya, Kyoko</creatorcontrib><creatorcontrib>Aoyama, Akihiro</creatorcontrib><creatorcontrib>Sato, Toshihiko</creatorcontrib><creatorcontrib>Sonobe, Makoto</creatorcontrib><creatorcontrib>Harada, Hiroshi</creatorcontrib><creatorcontrib>Date, Hiroshi</creatorcontrib><title>Hypoxia‐inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression</title><title>Cancer medicine (Malden, MA)</title><addtitle>Cancer Med</addtitle><description>Lung cancer treatment is difficult owing to chemoresistance. Hypoxia‐inducible factor 1 (HIF‐1) and HIF‐1‐induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF‐1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF‐1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF‐1α‐induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF‐1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF‐1α, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF‐1α expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF‐1‐dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF‐1α in A549 cells. HIF‐1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF‐1α, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF‐1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.
Hypoxia‐inducible factor 1 (HIF‐1) and carbonic anhydrase IX (CAIX) affected the chemosensitivity of lung cancer cell line and prognosis of lung cancer patients after induction chemoradiotherapy. Inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients.</description><subject>A549 Cells</subject><subject>Acidosis</subject><subject>Aged</subject><subject>Antigens, Neoplasm - metabolism</subject><subject>Cancer Biology</subject><subject>Cancer therapies</subject><subject>Carbonic anhydrase IX</subject><subject>Carbonic Anhydrase IX - metabolism</subject><subject>Carbonic anhydrases</subject><subject>Cell growth</subject><subject>Cell Hypoxia</subject><subject>Chemoradiotherapy</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Cytotoxicity</subject><subject>Drug Resistance, Neoplasm</subject><subject>Experiments</subject><subject>Female</subject><subject>Glucose transporter</subject><subject>Glucose Transporter Type 1 - metabolism</subject><subject>Glycolysis</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>hypoxia‐inducible factor 1</subject><subject>induction chemoradiotherapy</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer medicine (Malden, MA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sowa, Terumasa</au><au>Menju, Toshi</au><au>Chen‐Yoshikawa, Toyofumi F.</au><au>Takahashi, Koji</au><au>Nishikawa, Shigeto</au><au>Nakanishi, Takao</au><au>Shikuma, Kei</au><au>Motoyama, Hideki</au><au>Hijiya, Kyoko</au><au>Aoyama, Akihiro</au><au>Sato, Toshihiko</au><au>Sonobe, Makoto</au><au>Harada, Hiroshi</au><au>Date, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypoxia‐inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression</atitle><jtitle>Cancer medicine (Malden, MA)</jtitle><addtitle>Cancer Med</addtitle><date>2017-01</date><risdate>2017</risdate><volume>6</volume><issue>1</issue><spage>288</spage><epage>297</epage><pages>288-297</pages><issn>2045-7634</issn><eissn>2045-7634</eissn><abstract>Lung cancer treatment is difficult owing to chemoresistance. Hypoxia‐inducible factor 1 (HIF‐1) and HIF‐1‐induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF‐1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF‐1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF‐1α‐induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF‐1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF‐1α, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF‐1α expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF‐1‐dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF‐1α in A549 cells. HIF‐1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF‐1α, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF‐1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.
Hypoxia‐inducible factor 1 (HIF‐1) and carbonic anhydrase IX (CAIX) affected the chemosensitivity of lung cancer cell line and prognosis of lung cancer patients after induction chemoradiotherapy. Inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>28028936</pmid><doi>10.1002/cam4.991</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer medicine (Malden, MA), 2017-01, Vol.6 (1), p.288-297 |
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| source | MEDLINE; Wiley Journals; DOAJ Directory of Open Access Journals; Wiley Online Library Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | A549 Cells Acidosis Aged Antigens, Neoplasm - metabolism Cancer Biology Cancer therapies Carbonic anhydrase IX Carbonic Anhydrase IX - metabolism Carbonic anhydrases Cell growth Cell Hypoxia Chemoradiotherapy Chemoresistance Chemotherapy Cytotoxicity Drug Resistance, Neoplasm Experiments Female Glucose transporter Glucose Transporter Type 1 - metabolism Glycolysis Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - metabolism hypoxia‐inducible factor 1 induction chemoradiotherapy Lung cancer Lung Neoplasms - metabolism Lung Neoplasms - therapy Lymphatic system Male Manufacturers Metabolic pathways Metastasis Middle Aged Mutation Original Research Oxidative phosphorylation Patients Phosphorylation Plasmids Prognosis Studies Vinblastine - analogs & derivatives Vinblastine - pharmacology Vinblastine - therapeutic use Vinorelbine |
| title | Hypoxia‐inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T05%3A13%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hypoxia%E2%80%90inducible%20factor%201%20promotes%20chemoresistance%20of%20lung%20cancer%20by%20inducing%20carbonic%20anhydrase%20IX%20expression&rft.jtitle=Cancer%20medicine%20(Malden,%20MA)&rft.au=Sowa,%20Terumasa&rft.date=2017-01&rft.volume=6&rft.issue=1&rft.spage=288&rft.epage=297&rft.pages=288-297&rft.issn=2045-7634&rft.eissn=2045-7634&rft_id=info:doi/10.1002/cam4.991&rft_dat=%3Cproquest_pubme%3E2290723448%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2290723448&rft_id=info:pmid/28028936&rfr_iscdi=true |