Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling
Background Wisteria floribunda agglutinin (WFA) + Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about t...
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| Veröffentlicht in: | British journal of cancer 2020-09, Vol.123 (7), p.1145-1153 |
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| creator | Dolgormaa, Gantumur Harimoto, Norifumi Ishii, Norihiro Yamanaka, Takahiro Hagiwara, Kei Tsukagoshi, Mariko Igarashi, Takamichi Watanabe, Akira Kubo, Norio Araki, Kenichiro Handa, Tadashi Yokobori, Takehiko Oyama, Tetsunari Kuwano, Hiroyuki Shirabe, Ken |
| description | Background
Wisteria floribunda agglutinin (WFA)
+
Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC.
Methods
The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of
M2BP
were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated.
Results
M2BPGi and galectin-3 proteins co-localised in HCC cells, while
M2BP
mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC.
Conclusions
M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway. |
| doi_str_mv | 10.1038/s41416-020-0971-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7525442</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2420624815</sourcerecordid><originalsourceid>FETCH-LOGICAL-c620t-c664e39ccbf7742fbbb67b5ff06dfeabd0f4f7edc5ef0cc630f724dd40d1dfb33</originalsourceid><addsrcrecordid>eNp1kU1r3DAQhkVJabbb_oBciiCXXtxKsmzZl0II6QekBEp6FpI88irY0layl_jfV2bTpA30omGYZ97RzIvQGSUfKCmbj4lTTuuCMFKQVtBieYE2tCpZQRsmTtCGECJyhZFT9Dqlu5y2pBGv0GnJasYr0W7Q_XdlClZo5zvne7yPYQLncT8sRnnsUhghYvA75Q0kPO0Aq76PkJI7gM8BB4t3sFdTMDAM86AiNioa58OosF6wMpM7qGnVHm9vfuDkeq-GnL5BL60aErx9iFv08_PV7eXX4vrmy7fLi-vC1IxM-a05lK0x2grBmdVa10JX1pK6s6B0Ryy3AjpTgSXG1CWxgvGu46SjndVluUWfjrr7WY-ZAz9FNch9dKOKiwzKyX8r3u1kHw5SVKzinGWB9w8CMfyaIU1ydGldVnkIc5KMM5Kv2eTDb9H5M_QuzDHvu1KCt42oGc0UPVImhpQi2MfPUCJXX-XRV5l9lauvcsk97_7e4rHjj5EZYEcg5ZLvIT6N_r_qb-oysvE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2474987621</pqid></control><display><type>article</type><title>Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Dolgormaa, Gantumur ; Harimoto, Norifumi ; Ishii, Norihiro ; Yamanaka, Takahiro ; Hagiwara, Kei ; Tsukagoshi, Mariko ; Igarashi, Takamichi ; Watanabe, Akira ; Kubo, Norio ; Araki, Kenichiro ; Handa, Tadashi ; Yokobori, Takehiko ; Oyama, Tetsunari ; Kuwano, Hiroyuki ; Shirabe, Ken</creator><creatorcontrib>Dolgormaa, Gantumur ; Harimoto, Norifumi ; Ishii, Norihiro ; Yamanaka, Takahiro ; Hagiwara, Kei ; Tsukagoshi, Mariko ; Igarashi, Takamichi ; Watanabe, Akira ; Kubo, Norio ; Araki, Kenichiro ; Handa, Tadashi ; Yokobori, Takehiko ; Oyama, Tetsunari ; Kuwano, Hiroyuki ; Shirabe, Ken</creatorcontrib><description>Background
Wisteria floribunda agglutinin (WFA)
+
Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC.
Methods
The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of
M2BP
were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated.
Results
M2BPGi and galectin-3 proteins co-localised in HCC cells, while
M2BP
mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC.
Conclusions
M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-020-0971-y</identifier><identifier>PMID: 32624579</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1504/1610/4029 ; 692/4028/67/1504/1610/4029 ; Animals ; Antigens, Neoplasm - analysis ; Antigens, Neoplasm - physiology ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Disease Progression ; Drug Resistance ; Epidemiology ; Female ; Fibrosis ; Galectin 3 - analysis ; Galectin 3 - physiology ; Galectin-3 ; Gene expression ; Hepatocellular carcinoma ; Hepatocytes ; Humans ; Liver cancer ; Liver Neoplasms - pathology ; Membrane Glycoproteins - analysis ; Membrane Glycoproteins - physiology ; Mice ; Molecular Medicine ; Oncology ; Proteins ; Signal Transduction - physiology ; Stromal cells ; TOR protein ; TOR Serine-Threonine Kinases - physiology ; Transcriptomes ; Tumors ; Xenografts</subject><ispartof>British journal of cancer, 2020-09, Vol.123 (7), p.1145-1153</ispartof><rights>The Author(s), under exclusive licence to Cancer Research UK 2020</rights><rights>The Author(s), under exclusive licence to Cancer Research UK 2020. 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-c620t-c664e39ccbf7742fbbb67b5ff06dfeabd0f4f7edc5ef0cc630f724dd40d1dfb33</citedby><cites>FETCH-LOGICAL-c620t-c664e39ccbf7742fbbb67b5ff06dfeabd0f4f7edc5ef0cc630f724dd40d1dfb33</cites><orcidid>0000-0002-8085-2857</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/PMC7525442/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525442/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32624579$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dolgormaa, Gantumur</creatorcontrib><creatorcontrib>Harimoto, Norifumi</creatorcontrib><creatorcontrib>Ishii, Norihiro</creatorcontrib><creatorcontrib>Yamanaka, Takahiro</creatorcontrib><creatorcontrib>Hagiwara, Kei</creatorcontrib><creatorcontrib>Tsukagoshi, Mariko</creatorcontrib><creatorcontrib>Igarashi, Takamichi</creatorcontrib><creatorcontrib>Watanabe, Akira</creatorcontrib><creatorcontrib>Kubo, Norio</creatorcontrib><creatorcontrib>Araki, Kenichiro</creatorcontrib><creatorcontrib>Handa, Tadashi</creatorcontrib><creatorcontrib>Yokobori, Takehiko</creatorcontrib><creatorcontrib>Oyama, Tetsunari</creatorcontrib><creatorcontrib>Kuwano, Hiroyuki</creatorcontrib><creatorcontrib>Shirabe, Ken</creatorcontrib><title>Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Wisteria floribunda agglutinin (WFA)
+
Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC.
Methods
The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of
M2BP
were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated.
Results
M2BPGi and galectin-3 proteins co-localised in HCC cells, while
M2BP
mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC.
Conclusions
M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.</description><subject>631/67/1504/1610/4029</subject><subject>692/4028/67/1504/1610/4029</subject><subject>Animals</subject><subject>Antigens, Neoplasm - analysis</subject><subject>Antigens, Neoplasm - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Disease Progression</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Galectin 3 - analysis</subject><subject>Galectin 3 - physiology</subject><subject>Galectin-3</subject><subject>Gene expression</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - pathology</subject><subject>Membrane Glycoproteins - analysis</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Mice</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Proteins</subject><subject>Signal Transduction - physiology</subject><subject>Stromal cells</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - physiology</subject><subject>Transcriptomes</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1r3DAQhkVJabbb_oBciiCXXtxKsmzZl0II6QekBEp6FpI88irY0layl_jfV2bTpA30omGYZ97RzIvQGSUfKCmbj4lTTuuCMFKQVtBieYE2tCpZQRsmTtCGECJyhZFT9Dqlu5y2pBGv0GnJasYr0W7Q_XdlClZo5zvne7yPYQLncT8sRnnsUhghYvA75Q0kPO0Aq76PkJI7gM8BB4t3sFdTMDAM86AiNioa58OosF6wMpM7qGnVHm9vfuDkeq-GnL5BL60aErx9iFv08_PV7eXX4vrmy7fLi-vC1IxM-a05lK0x2grBmdVa10JX1pK6s6B0Ryy3AjpTgSXG1CWxgvGu46SjndVluUWfjrr7WY-ZAz9FNch9dKOKiwzKyX8r3u1kHw5SVKzinGWB9w8CMfyaIU1ydGldVnkIc5KMM5Kv2eTDb9H5M_QuzDHvu1KCt42oGc0UPVImhpQi2MfPUCJXX-XRV5l9lauvcsk97_7e4rHjj5EZYEcg5ZLvIT6N_r_qb-oysvE</recordid><startdate>20200929</startdate><enddate>20200929</enddate><creator>Dolgormaa, Gantumur</creator><creator>Harimoto, Norifumi</creator><creator>Ishii, Norihiro</creator><creator>Yamanaka, Takahiro</creator><creator>Hagiwara, Kei</creator><creator>Tsukagoshi, Mariko</creator><creator>Igarashi, Takamichi</creator><creator>Watanabe, Akira</creator><creator>Kubo, Norio</creator><creator>Araki, Kenichiro</creator><creator>Handa, Tadashi</creator><creator>Yokobori, Takehiko</creator><creator>Oyama, Tetsunari</creator><creator>Kuwano, Hiroyuki</creator><creator>Shirabe, Ken</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8085-2857</orcidid></search><sort><creationdate>20200929</creationdate><title>Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling</title><author>Dolgormaa, Gantumur ; Harimoto, Norifumi ; Ishii, Norihiro ; Yamanaka, Takahiro ; Hagiwara, Kei ; Tsukagoshi, Mariko ; Igarashi, Takamichi ; Watanabe, Akira ; Kubo, Norio ; Araki, Kenichiro ; Handa, Tadashi ; Yokobori, Takehiko ; Oyama, Tetsunari ; Kuwano, Hiroyuki ; Shirabe, Ken</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c620t-c664e39ccbf7742fbbb67b5ff06dfeabd0f4f7edc5ef0cc630f724dd40d1dfb33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/67/1504/1610/4029</topic><topic>692/4028/67/1504/1610/4029</topic><topic>Animals</topic><topic>Antigens, Neoplasm - analysis</topic><topic>Antigens, Neoplasm - physiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Disease Progression</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Galectin 3 - analysis</topic><topic>Galectin 3 - physiology</topic><topic>Galectin-3</topic><topic>Gene expression</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - pathology</topic><topic>Membrane Glycoproteins - analysis</topic><topic>Membrane Glycoproteins - physiology</topic><topic>Mice</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Proteins</topic><topic>Signal Transduction - physiology</topic><topic>Stromal cells</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - physiology</topic><topic>Transcriptomes</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dolgormaa, Gantumur</creatorcontrib><creatorcontrib>Harimoto, Norifumi</creatorcontrib><creatorcontrib>Ishii, Norihiro</creatorcontrib><creatorcontrib>Yamanaka, Takahiro</creatorcontrib><creatorcontrib>Hagiwara, Kei</creatorcontrib><creatorcontrib>Tsukagoshi, Mariko</creatorcontrib><creatorcontrib>Igarashi, Takamichi</creatorcontrib><creatorcontrib>Watanabe, Akira</creatorcontrib><creatorcontrib>Kubo, Norio</creatorcontrib><creatorcontrib>Araki, Kenichiro</creatorcontrib><creatorcontrib>Handa, Tadashi</creatorcontrib><creatorcontrib>Yokobori, Takehiko</creatorcontrib><creatorcontrib>Oyama, Tetsunari</creatorcontrib><creatorcontrib>Kuwano, Hiroyuki</creatorcontrib><creatorcontrib>Shirabe, Ken</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>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</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>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>British Nursing Database</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dolgormaa, Gantumur</au><au>Harimoto, Norifumi</au><au>Ishii, Norihiro</au><au>Yamanaka, Takahiro</au><au>Hagiwara, Kei</au><au>Tsukagoshi, Mariko</au><au>Igarashi, Takamichi</au><au>Watanabe, Akira</au><au>Kubo, Norio</au><au>Araki, Kenichiro</au><au>Handa, Tadashi</au><au>Yokobori, Takehiko</au><au>Oyama, Tetsunari</au><au>Kuwano, Hiroyuki</au><au>Shirabe, Ken</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2020-09-29</date><risdate>2020</risdate><volume>123</volume><issue>7</issue><spage>1145</spage><epage>1153</epage><pages>1145-1153</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
Wisteria floribunda agglutinin (WFA)
+
Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC.
Methods
The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of
M2BP
were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated.
Results
M2BPGi and galectin-3 proteins co-localised in HCC cells, while
M2BP
mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC.
Conclusions
M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32624579</pmid><doi>10.1038/s41416-020-0971-y</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8085-2857</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/1504/1610/4029 692/4028/67/1504/1610/4029 Animals Antigens, Neoplasm - analysis Antigens, Neoplasm - physiology Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Hepatocellular - pathology Cell Line, Tumor Disease Progression Drug Resistance Epidemiology Female Fibrosis Galectin 3 - analysis Galectin 3 - physiology Galectin-3 Gene expression Hepatocellular carcinoma Hepatocytes Humans Liver cancer Liver Neoplasms - pathology Membrane Glycoproteins - analysis Membrane Glycoproteins - physiology Mice Molecular Medicine Oncology Proteins Signal Transduction - physiology Stromal cells TOR protein TOR Serine-Threonine Kinases - physiology Transcriptomes Tumors Xenografts |
| title | Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling |
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