OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2
Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, the mechanisms of metastasis in pancreatic cancer remain unclear. Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like scavenger receptor that recognizes several lig...
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| Veröffentlicht in: | Molecular cancer research 2020-05, Vol.18 (5), p.685-697 |
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| creator | Yang, Gang Xiong, Guangbing Feng, Mengyu Zhao, Fangyu Qiu, Jiangdong Liu, Yueze Cao, Zhe Wang, Huanyu Yang, Jinshou You, Lei Zheng, Lianfang Zhang, Taiping Zhao, Yupei |
| description | Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, the mechanisms of metastasis in pancreatic cancer remain unclear. Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like scavenger receptor that recognizes several ligands, such as oxidized low-density lipoprotein, was previously reported in cardiovascular and metabolic diseases. The role and mechanism of OLR1 in pancreatic cancer is unclear. In this study, we found that OLR1 expression was significantly higher in pancreatic cancer tissues than that in adjacent normal tissues and closely associated with reduced overall survival. OLR1 promoted proliferation and metastasis of pancreatic cancer cells
and
. Mechanistically, OLR1 increased HMGA2 transcription by upregulating c-Myc expression to promote the metastasis of pancreatic cancer cells. In addition, patients with pancreatic cancer with high expression of OLR1-c-Myc-HMGA2 axis showed worse prognosis compared with patients with low expression of OLR1-c-Myc-HMGA2 axis. IMPLICATIONS: Our findings suggested that the OLR1-c-Myc-HMGA2 axis promotes metastasis of pancreatic cancer cells and may serve as potential therapeutic targets and prognosis markers for patients with pancreatic cancer. |
| doi_str_mv | 10.1158/1541-7786.mcr-19-0718 |
| format | Article |
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and
. Mechanistically, OLR1 increased HMGA2 transcription by upregulating c-Myc expression to promote the metastasis of pancreatic cancer cells. In addition, patients with pancreatic cancer with high expression of OLR1-c-Myc-HMGA2 axis showed worse prognosis compared with patients with low expression of OLR1-c-Myc-HMGA2 axis. IMPLICATIONS: Our findings suggested that the OLR1-c-Myc-HMGA2 axis promotes metastasis of pancreatic cancer cells and may serve as potential therapeutic targets and prognosis markers for patients with pancreatic cancer.</description><identifier>ISSN: 1541-7786</identifier><identifier>EISSN: 1557-3125</identifier><identifier>DOI: 10.1158/1541-7786.mcr-19-0718</identifier><identifier>PMID: 32019809</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Apoptosis ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Cell Movement ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; HMGA2 Protein - genetics ; HMGA2 Protein - metabolism ; Humans ; Male ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Metastasis ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Prognosis ; Proto-Oncogene Proteins c-myc - genetics ; Proto-Oncogene Proteins c-myc - metabolism ; Scavenger Receptors, Class E - genetics ; Scavenger Receptors, Class E - metabolism ; Survival Rate ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays</subject><ispartof>Molecular cancer research, 2020-05, Vol.18 (5), p.685-697</ispartof><rights>2020 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-40fa15db8093eb302abe9b2e25f4592bce81b815014dc9ba434f19dd4e610c623</citedby><cites>FETCH-LOGICAL-c422t-40fa15db8093eb302abe9b2e25f4592bce81b815014dc9ba434f19dd4e610c623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32019809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Gang</creatorcontrib><creatorcontrib>Xiong, Guangbing</creatorcontrib><creatorcontrib>Feng, Mengyu</creatorcontrib><creatorcontrib>Zhao, Fangyu</creatorcontrib><creatorcontrib>Qiu, Jiangdong</creatorcontrib><creatorcontrib>Liu, Yueze</creatorcontrib><creatorcontrib>Cao, Zhe</creatorcontrib><creatorcontrib>Wang, Huanyu</creatorcontrib><creatorcontrib>Yang, Jinshou</creatorcontrib><creatorcontrib>You, Lei</creatorcontrib><creatorcontrib>Zheng, Lianfang</creatorcontrib><creatorcontrib>Zhang, Taiping</creatorcontrib><creatorcontrib>Zhao, Yupei</creatorcontrib><title>OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2</title><title>Molecular cancer research</title><addtitle>Mol Cancer Res</addtitle><description>Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, the mechanisms of metastasis in pancreatic cancer remain unclear. Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like scavenger receptor that recognizes several ligands, such as oxidized low-density lipoprotein, was previously reported in cardiovascular and metabolic diseases. The role and mechanism of OLR1 in pancreatic cancer is unclear. In this study, we found that OLR1 expression was significantly higher in pancreatic cancer tissues than that in adjacent normal tissues and closely associated with reduced overall survival. OLR1 promoted proliferation and metastasis of pancreatic cancer cells
and
. Mechanistically, OLR1 increased HMGA2 transcription by upregulating c-Myc expression to promote the metastasis of pancreatic cancer cells. In addition, patients with pancreatic cancer with high expression of OLR1-c-Myc-HMGA2 axis showed worse prognosis compared with patients with low expression of OLR1-c-Myc-HMGA2 axis. IMPLICATIONS: Our findings suggested that the OLR1-c-Myc-HMGA2 axis promotes metastasis of pancreatic cancer cells and may serve as potential therapeutic targets and prognosis markers for patients with pancreatic cancer.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>HMGA2 Protein - genetics</subject><subject>HMGA2 Protein - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Scavenger Receptors, Class E - genetics</subject><subject>Scavenger Receptors, Class E - metabolism</subject><subject>Survival Rate</subject><subject>Tumor Cells, Cultured</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1541-7786</issn><issn>1557-3125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF1LwzAUhoMobk5_gpJLbzpz0qRtLseY22BlY8zrkKanUFk_TDpx_95Wp3DgvJzzng8eQh6BTQFk8gJSQBDHSTStrAtABSyG5IqMQco4CIHL60FfPCNy5_07Y5xBHN2SUdgLlTA1Jvl2swe6c03VdOjpztTWoelKS-e9REdT7Izvo_T0szR0_dP3mFMbpGdLF1-tQ-_LpqamzunBmdpbV7bdUGkKukqXM35Pbgpz9PhwyRPy9ro4zFfBZrtcz2ebwArOu0CwwoDMs_6xELOQcZOhyjhyWQipeGYxgSwByUDkVmVGhKIAlecCI2A24uGEPP_ubV3zcULf6ar0Fo9HU2Nz8pqHEkQCPIp6q_y1Wtd477DQrSsr484amB4A6wGeHuDpdL7XoPQAuJ97upw4ZRXm_1N_RMNv_x52nA</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Yang, Gang</creator><creator>Xiong, Guangbing</creator><creator>Feng, Mengyu</creator><creator>Zhao, Fangyu</creator><creator>Qiu, Jiangdong</creator><creator>Liu, Yueze</creator><creator>Cao, Zhe</creator><creator>Wang, Huanyu</creator><creator>Yang, Jinshou</creator><creator>You, Lei</creator><creator>Zheng, Lianfang</creator><creator>Zhang, Taiping</creator><creator>Zhao, Yupei</creator><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></search><sort><creationdate>202005</creationdate><title>OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2</title><author>Yang, Gang ; Xiong, Guangbing ; Feng, Mengyu ; Zhao, Fangyu ; Qiu, Jiangdong ; Liu, Yueze ; Cao, Zhe ; Wang, Huanyu ; Yang, Jinshou ; You, Lei ; Zheng, Lianfang ; Zhang, Taiping ; Zhao, Yupei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-40fa15db8093eb302abe9b2e25f4592bce81b815014dc9ba434f19dd4e610c623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>HMGA2 Protein - genetics</topic><topic>HMGA2 Protein - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Scavenger Receptors, Class E - genetics</topic><topic>Scavenger Receptors, Class E - metabolism</topic><topic>Survival Rate</topic><topic>Tumor Cells, Cultured</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Gang</creatorcontrib><creatorcontrib>Xiong, Guangbing</creatorcontrib><creatorcontrib>Feng, Mengyu</creatorcontrib><creatorcontrib>Zhao, Fangyu</creatorcontrib><creatorcontrib>Qiu, Jiangdong</creatorcontrib><creatorcontrib>Liu, Yueze</creatorcontrib><creatorcontrib>Cao, Zhe</creatorcontrib><creatorcontrib>Wang, Huanyu</creatorcontrib><creatorcontrib>Yang, Jinshou</creatorcontrib><creatorcontrib>You, Lei</creatorcontrib><creatorcontrib>Zheng, Lianfang</creatorcontrib><creatorcontrib>Zhang, Taiping</creatorcontrib><creatorcontrib>Zhao, Yupei</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><jtitle>Molecular cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Gang</au><au>Xiong, Guangbing</au><au>Feng, Mengyu</au><au>Zhao, Fangyu</au><au>Qiu, Jiangdong</au><au>Liu, Yueze</au><au>Cao, Zhe</au><au>Wang, Huanyu</au><au>Yang, Jinshou</au><au>You, Lei</au><au>Zheng, Lianfang</au><au>Zhang, Taiping</au><au>Zhao, Yupei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2</atitle><jtitle>Molecular cancer research</jtitle><addtitle>Mol Cancer Res</addtitle><date>2020-05</date><risdate>2020</risdate><volume>18</volume><issue>5</issue><spage>685</spage><epage>697</epage><pages>685-697</pages><issn>1541-7786</issn><eissn>1557-3125</eissn><abstract>Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, the mechanisms of metastasis in pancreatic cancer remain unclear. Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like scavenger receptor that recognizes several ligands, such as oxidized low-density lipoprotein, was previously reported in cardiovascular and metabolic diseases. The role and mechanism of OLR1 in pancreatic cancer is unclear. In this study, we found that OLR1 expression was significantly higher in pancreatic cancer tissues than that in adjacent normal tissues and closely associated with reduced overall survival. OLR1 promoted proliferation and metastasis of pancreatic cancer cells
and
. Mechanistically, OLR1 increased HMGA2 transcription by upregulating c-Myc expression to promote the metastasis of pancreatic cancer cells. In addition, patients with pancreatic cancer with high expression of OLR1-c-Myc-HMGA2 axis showed worse prognosis compared with patients with low expression of OLR1-c-Myc-HMGA2 axis. IMPLICATIONS: Our findings suggested that the OLR1-c-Myc-HMGA2 axis promotes metastasis of pancreatic cancer cells and may serve as potential therapeutic targets and prognosis markers for patients with pancreatic cancer.</abstract><cop>United States</cop><pmid>32019809</pmid><doi>10.1158/1541-7786.mcr-19-0718</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Cell Movement Cell Proliferation Female Gene Expression Regulation, Neoplastic HMGA2 Protein - genetics HMGA2 Protein - metabolism Humans Male Mice Mice, Nude Middle Aged Neoplasm Metastasis Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Prognosis Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism Scavenger Receptors, Class E - genetics Scavenger Receptors, Class E - metabolism Survival Rate Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| title | OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2 |
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