Crabp2 Promotes Metastasis of Lung Cancer Cells via HuR and Integrin β1/FAK/ERK Signaling
Increased Crabp2 levels have been found in various types of cancer, and are associated with poor patients’ survival. Although Crabp2 is found to be overexpressed in lung cancer, its role in metastasis of lung cancer is unclear. In this study, Crabp2 was overexpressed in high-metastatic C10F4 than lo...
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| description | Increased Crabp2 levels have been found in various types of cancer, and are associated with poor patients’ survival. Although Crabp2 is found to be overexpressed in lung cancer, its role in metastasis of lung cancer is unclear. In this study, Crabp2 was overexpressed in high-metastatic C10F4 than low-metastatic lung cancer cells. Analysis of clinical samples revealed that high CRABP2 levels were correlated with lymph node metastases, poor overall survival, and increased recurrence. Knockdown of Crabp2 decreased migration, invasion, anoikis resistance, and
in vivo
metastasis. Crabp2 was co-immunoprecipitated with HuR, and overexpression of Crabp2 increased HuR levels, which promoted integrin β1/FAK/ERK signaling. Inhibition of HuR or integrin β1/FAK/ERK signaling reversed the promoting effect of Crabp2 in migration, invasion, and anoikis resistance. Knockdown of Crabp2 further inhibited the growth of cancer cells as compared with that by gemcitabine or irinotecan alone. The expression of Crabp2 in human lung tumors was correlated with stress marker CHOP. In conclusion, our findings have identified the promoting role of Crabp2 in anoikis resistance and metastasis. CRABP2 may serve as a prognostic marker and targeting CRABP2 may be exploited as a modality to reduce metastasis. |
| doi_str_mv | 10.1038/s41598-018-37443-4 |
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in vivo
metastasis. Crabp2 was co-immunoprecipitated with HuR, and overexpression of Crabp2 increased HuR levels, which promoted integrin β1/FAK/ERK signaling. Inhibition of HuR or integrin β1/FAK/ERK signaling reversed the promoting effect of Crabp2 in migration, invasion, and anoikis resistance. Knockdown of Crabp2 further inhibited the growth of cancer cells as compared with that by gemcitabine or irinotecan alone. The expression of Crabp2 in human lung tumors was correlated with stress marker CHOP. In conclusion, our findings have identified the promoting role of Crabp2 in anoikis resistance and metastasis. CRABP2 may serve as a prognostic marker and targeting CRABP2 may be exploited as a modality to reduce metastasis.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-37443-4</identifier><identifier>PMID: 30696915</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/105 ; 13/109 ; 13/51 ; 13/89 ; 14/63 ; 45/90 ; 631/67/1612 ; 631/67/322 ; 64/60 ; 82/29 ; Anoikis ; Extracellular signal-regulated kinase ; Gemcitabine ; Humanities and Social Sciences ; HuR protein ; Irinotecan ; Lung cancer ; Lymph nodes ; Metastases ; Metastasis ; multidisciplinary ; Science ; Science (multidisciplinary) ; Tumors</subject><ispartof>Scientific reports, 2019-01, Vol.9 (1), p.845-845, Article 845</ispartof><rights>The Author(s) 2019</rights><rights>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-c540t-1e89f0cf83d32ba017afd246b865aa15baecb63f60291f533ced9b379ce7218d3</citedby><cites>FETCH-LOGICAL-c540t-1e89f0cf83d32ba017afd246b865aa15baecb63f60291f533ced9b379ce7218d3</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/PMC6351595/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351595/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30696915$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Jun-I</creatorcontrib><creatorcontrib>Lin, Yi-Pei</creatorcontrib><creatorcontrib>Tseng, Chien-Wei</creatorcontrib><creatorcontrib>Chen, Hui-Jane</creatorcontrib><creatorcontrib>Wang, Lu-Hai</creatorcontrib><title>Crabp2 Promotes Metastasis of Lung Cancer Cells via HuR and Integrin β1/FAK/ERK Signaling</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Increased Crabp2 levels have been found in various types of cancer, and are associated with poor patients’ survival. Although Crabp2 is found to be overexpressed in lung cancer, its role in metastasis of lung cancer is unclear. In this study, Crabp2 was overexpressed in high-metastatic C10F4 than low-metastatic lung cancer cells. Analysis of clinical samples revealed that high CRABP2 levels were correlated with lymph node metastases, poor overall survival, and increased recurrence. Knockdown of Crabp2 decreased migration, invasion, anoikis resistance, and
in vivo
metastasis. Crabp2 was co-immunoprecipitated with HuR, and overexpression of Crabp2 increased HuR levels, which promoted integrin β1/FAK/ERK signaling. Inhibition of HuR or integrin β1/FAK/ERK signaling reversed the promoting effect of Crabp2 in migration, invasion, and anoikis resistance. Knockdown of Crabp2 further inhibited the growth of cancer cells as compared with that by gemcitabine or irinotecan alone. The expression of Crabp2 in human lung tumors was correlated with stress marker CHOP. In conclusion, our findings have identified the promoting role of Crabp2 in anoikis resistance and metastasis. CRABP2 may serve as a prognostic marker and targeting CRABP2 may be exploited as a modality to reduce metastasis.</description><subject>13/105</subject><subject>13/109</subject><subject>13/51</subject><subject>13/89</subject><subject>14/63</subject><subject>45/90</subject><subject>631/67/1612</subject><subject>631/67/322</subject><subject>64/60</subject><subject>82/29</subject><subject>Anoikis</subject><subject>Extracellular signal-regulated kinase</subject><subject>Gemcitabine</subject><subject>Humanities and Social Sciences</subject><subject>HuR protein</subject><subject>Irinotecan</subject><subject>Lung cancer</subject><subject>Lymph nodes</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>multidisciplinary</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Tumors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1KHTEYhkOpVFFvoIsScNPNePI_k40gg394xOLPxk3IZDLTyJzkmMwI3pYX4jU19ahVFw2BBL7ne7-8eQH4jtEuRrSaJYa5rAqEq4KWjNGCfQEbBDFeEErI13f3dbCd0i3KixPJsPwG1ikSUkjMN8BNHXWzJPBXDIsw2gTP7KhT3i7B0MH55HtYa29shLUdhgTvnYbH0wXUvoUnfrR9dB4-PeLZ4f7p7ODiFF663uvB-X4LrHV6SHb75dwE14cHV_VxMT8_Oqn354XhDI0FtpXskOkq2lLSaIRL3bWEiaYSXGvMG21NI2gnEJG445Qa28qGltLYkuCqpZtgb6W7nJqFbY31Y9SDWka30PFBBe3Ux4p3v1Uf7pWgPP8hzwI_XwRiuJtsGtXCJZPdam_DlBTBpWSipBxldOcTehummP0-U0SICnGRKbKiTAwpRdu9PQYj9Tc9tUpP5fTUc3qK5aYf7228tbxmlQG6AlIu-d7Gf7P_I_sH1DmkwA</recordid><startdate>20190129</startdate><enddate>20190129</enddate><creator>Wu, Jun-I</creator><creator>Lin, Yi-Pei</creator><creator>Tseng, Chien-Wei</creator><creator>Chen, Hui-Jane</creator><creator>Wang, Lu-Hai</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</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>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190129</creationdate><title>Crabp2 Promotes Metastasis of Lung Cancer Cells via HuR and Integrin β1/FAK/ERK Signaling</title><author>Wu, Jun-I ; Lin, Yi-Pei ; Tseng, Chien-Wei ; Chen, Hui-Jane ; Wang, Lu-Hai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-1e89f0cf83d32ba017afd246b865aa15baecb63f60291f533ced9b379ce7218d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/105</topic><topic>13/109</topic><topic>13/51</topic><topic>13/89</topic><topic>14/63</topic><topic>45/90</topic><topic>631/67/1612</topic><topic>631/67/322</topic><topic>64/60</topic><topic>82/29</topic><topic>Anoikis</topic><topic>Extracellular signal-regulated kinase</topic><topic>Gemcitabine</topic><topic>Humanities and Social Sciences</topic><topic>HuR protein</topic><topic>Irinotecan</topic><topic>Lung cancer</topic><topic>Lymph nodes</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>multidisciplinary</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Jun-I</creatorcontrib><creatorcontrib>Lin, Yi-Pei</creatorcontrib><creatorcontrib>Tseng, Chien-Wei</creatorcontrib><creatorcontrib>Chen, Hui-Jane</creatorcontrib><creatorcontrib>Wang, Lu-Hai</creatorcontrib><collection>Springer Nature OA Free Journals</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>Medical 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 One Sustainability</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>Medical Database</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Jun-I</au><au>Lin, Yi-Pei</au><au>Tseng, Chien-Wei</au><au>Chen, Hui-Jane</au><au>Wang, Lu-Hai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Crabp2 Promotes Metastasis of Lung Cancer Cells via HuR and Integrin β1/FAK/ERK Signaling</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-01-29</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>845</spage><epage>845</epage><pages>845-845</pages><artnum>845</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Increased Crabp2 levels have been found in various types of cancer, and are associated with poor patients’ survival. Although Crabp2 is found to be overexpressed in lung cancer, its role in metastasis of lung cancer is unclear. In this study, Crabp2 was overexpressed in high-metastatic C10F4 than low-metastatic lung cancer cells. Analysis of clinical samples revealed that high CRABP2 levels were correlated with lymph node metastases, poor overall survival, and increased recurrence. Knockdown of Crabp2 decreased migration, invasion, anoikis resistance, and
in vivo
metastasis. Crabp2 was co-immunoprecipitated with HuR, and overexpression of Crabp2 increased HuR levels, which promoted integrin β1/FAK/ERK signaling. Inhibition of HuR or integrin β1/FAK/ERK signaling reversed the promoting effect of Crabp2 in migration, invasion, and anoikis resistance. Knockdown of Crabp2 further inhibited the growth of cancer cells as compared with that by gemcitabine or irinotecan alone. The expression of Crabp2 in human lung tumors was correlated with stress marker CHOP. In conclusion, our findings have identified the promoting role of Crabp2 in anoikis resistance and metastasis. CRABP2 may serve as a prognostic marker and targeting CRABP2 may be exploited as a modality to reduce metastasis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30696915</pmid><doi>10.1038/s41598-018-37443-4</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/105 13/109 13/51 13/89 14/63 45/90 631/67/1612 631/67/322 64/60 82/29 Anoikis Extracellular signal-regulated kinase Gemcitabine Humanities and Social Sciences HuR protein Irinotecan Lung cancer Lymph nodes Metastases Metastasis multidisciplinary Science Science (multidisciplinary) Tumors |
| title | Crabp2 Promotes Metastasis of Lung Cancer Cells via HuR and Integrin β1/FAK/ERK Signaling |
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