Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box―Binding Protein-1 Promotes Prostate Cancer Progression
Y-box-binding protein-1 (YB-1) is known to conduct various functions related to cell proliferation, anti-apoptosis, epithelial-mesenchymal transition, and castration resistance in prostate cancer. However, it is still unknown how YB-1 affects cancer biology, especially its correlations with the mito...
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| Veröffentlicht in: | Clinical cancer research 2013-09, Vol.19 (17), p.4638-4650 |
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| creator | IMADA, Kenjiro SHIOTA, Masaki KOHASHI, Kenichi KUROIWA, Kentaro SONG, Yoohyun SUGIMOTO, Masaaki NAITO, Seiji ODA, Yoshinao |
| description | Y-box-binding protein-1 (YB-1) is known to conduct various functions related to cell proliferation, anti-apoptosis, epithelial-mesenchymal transition, and castration resistance in prostate cancer. However, it is still unknown how YB-1 affects cancer biology, especially its correlations with the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, we aimed to examine the interaction between YB-1 and the MAPK pathway in prostate cancer.
Quantitative real-time PCR, Western blotting, and co-immunoprecipitation assay were conducted in prostate cancer cells. YB-1, phosphorylated YB-1 (p-YB-1), and ERK2 protein expressions in 165 clinical specimens of prostate cancer were investigated by immunohistochemistry. YB-1, p-YB-1, and ERK2 nuclear expressions were compared with clinicopathologic characteristics and patient prognoses.
EGF upregulated p-YB-1, whereas MEK inhibitor (U0126, PD98059) decreased p-YB-1. Inversely, silencing of YB-1 using siRNA decreased the expression of ERK2 and phosphorylated MEK, ERK1/2, and RSK. Furthermore, YB-1 interacted with ERK2 and Raf-1 and regulated their expressions, through the proteasomal pathway. Immunohistochemical staining showed a significant correlation among the nuclear expressions of YB-1, p-YB-1, and ERK2. The Cox proportional hazards model revealed that high ERK2 expression was an independent prognostic factor [HR, 7.947; 95% confidence interval (CI), 3.527-20.508; P |
| doi_str_mv | 10.1158/1078-0432.CCR-12-3705 |
| format | Article |
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Quantitative real-time PCR, Western blotting, and co-immunoprecipitation assay were conducted in prostate cancer cells. YB-1, phosphorylated YB-1 (p-YB-1), and ERK2 protein expressions in 165 clinical specimens of prostate cancer were investigated by immunohistochemistry. YB-1, p-YB-1, and ERK2 nuclear expressions were compared with clinicopathologic characteristics and patient prognoses.
EGF upregulated p-YB-1, whereas MEK inhibitor (U0126, PD98059) decreased p-YB-1. Inversely, silencing of YB-1 using siRNA decreased the expression of ERK2 and phosphorylated MEK, ERK1/2, and RSK. Furthermore, YB-1 interacted with ERK2 and Raf-1 and regulated their expressions, through the proteasomal pathway. Immunohistochemical staining showed a significant correlation among the nuclear expressions of YB-1, p-YB-1, and ERK2. The Cox proportional hazards model revealed that high ERK2 expression was an independent prognostic factor [HR, 7.947; 95% confidence interval (CI), 3.527-20.508; P<0.0001].
We revealed the functional relationship between YB-1 and MAPK signaling and its biochemical relevance to the progression of prostate cancer. In addition, ERK2 expression was an independent prognostic factor. These findings suggest that both the ERK pathway and YB-1 may be promising molecular targets for prostate cancer diagnosis and therapeutics.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-12-3705</identifier><identifier>PMID: 23838318</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Biological and medical sciences ; Carcinogenesis ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Gynecology. Andrology. Obstetrics ; Humans ; Male ; Male genital diseases ; MAP Kinase Signaling System - genetics ; Medical sciences ; Nephrology. Urinary tract diseases ; Phosphorylation ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; raf Kinases - genetics ; Signal Transduction ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland ; Y-Box-Binding Protein 1 - genetics ; Y-Box-Binding Protein 1 - metabolism</subject><ispartof>Clinical cancer research, 2013-09, Vol.19 (17), p.4638-4650</ispartof><rights>2014 INIST-CNRS</rights><rights>2013 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-ca454f3fcf95b31228ada20bc2f1ad0f92c40a02184cb09a51fef04a66950b0a3</citedby><cites>FETCH-LOGICAL-c587t-ca454f3fcf95b31228ada20bc2f1ad0f92c40a02184cb09a51fef04a66950b0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27716435$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23838318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>IMADA, Kenjiro</creatorcontrib><creatorcontrib>SHIOTA, Masaki</creatorcontrib><creatorcontrib>KOHASHI, Kenichi</creatorcontrib><creatorcontrib>KUROIWA, Kentaro</creatorcontrib><creatorcontrib>SONG, Yoohyun</creatorcontrib><creatorcontrib>SUGIMOTO, Masaaki</creatorcontrib><creatorcontrib>NAITO, Seiji</creatorcontrib><creatorcontrib>ODA, Yoshinao</creatorcontrib><title>Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box―Binding Protein-1 Promotes Prostate Cancer Progression</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Y-box-binding protein-1 (YB-1) is known to conduct various functions related to cell proliferation, anti-apoptosis, epithelial-mesenchymal transition, and castration resistance in prostate cancer. However, it is still unknown how YB-1 affects cancer biology, especially its correlations with the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, we aimed to examine the interaction between YB-1 and the MAPK pathway in prostate cancer.
Quantitative real-time PCR, Western blotting, and co-immunoprecipitation assay were conducted in prostate cancer cells. YB-1, phosphorylated YB-1 (p-YB-1), and ERK2 protein expressions in 165 clinical specimens of prostate cancer were investigated by immunohistochemistry. YB-1, p-YB-1, and ERK2 nuclear expressions were compared with clinicopathologic characteristics and patient prognoses.
EGF upregulated p-YB-1, whereas MEK inhibitor (U0126, PD98059) decreased p-YB-1. Inversely, silencing of YB-1 using siRNA decreased the expression of ERK2 and phosphorylated MEK, ERK1/2, and RSK. Furthermore, YB-1 interacted with ERK2 and Raf-1 and regulated their expressions, through the proteasomal pathway. Immunohistochemical staining showed a significant correlation among the nuclear expressions of YB-1, p-YB-1, and ERK2. The Cox proportional hazards model revealed that high ERK2 expression was an independent prognostic factor [HR, 7.947; 95% confidence interval (CI), 3.527-20.508; P<0.0001].
We revealed the functional relationship between YB-1 and MAPK signaling and its biochemical relevance to the progression of prostate cancer. In addition, ERK2 expression was an independent prognostic factor. These findings suggest that both the ERK pathway and YB-1 may be promising molecular targets for prostate cancer diagnosis and therapeutics.</description><subject>Biological and medical sciences</subject><subject>Carcinogenesis</subject><subject>Cell Proliferation</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>MAP Kinase Signaling System - genetics</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Phosphorylation</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>raf Kinases - genetics</subject><subject>Signal Transduction</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. Prostate gland</subject><subject>Y-Box-Binding Protein 1 - genetics</subject><subject>Y-Box-Binding Protein 1 - metabolism</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtu1DAUhi0EoqXlEUDZIHXjzjm-TJIljYaL2go0bResrBPHHgVlnGInAna8BC_Ik-CoU5AX_m1956KPsVcI54i6WiGUFQclxXnTbDkKLkvQT9gxal1yKdb6ac6PzBF7kdJXAFQI6jk7ErLKB6tjFq_naaah2LrdPNDUj6Fo3fTduVBsya-uN5erzfayuOl3gYY-7AoKXfGFX4w__vz6fdGHbvn7HMfJ9YHjkvY5pyWkiSZXNBSsi8t7F11KecApe-ZpSO7l4T5hd-82t80HfvXp_cfm7RW3uionbklp5aW3vtatRCEq6khAa4VH6sDXwiogEFgp20JNGr3zoGi9rjW0QPKEnT30vY_jt9mlyez7ZN0wUHDjnAwqCbIutdQZ1Q-ozWun6Ly5j_2e4k-DYBbdZlFpFpUm6zYozKI7170-jJjbvev-VT36zcCbA0DJ0uBjttGn_1xZ4lrlBf4Cs_uJTQ</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>IMADA, Kenjiro</creator><creator>SHIOTA, Masaki</creator><creator>KOHASHI, Kenichi</creator><creator>KUROIWA, Kentaro</creator><creator>SONG, Yoohyun</creator><creator>SUGIMOTO, Masaaki</creator><creator>NAITO, Seiji</creator><creator>ODA, Yoshinao</creator><general>American Association for Cancer Research</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>20130901</creationdate><title>Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box―Binding Protein-1 Promotes Prostate Cancer Progression</title><author>IMADA, Kenjiro ; SHIOTA, Masaki ; KOHASHI, Kenichi ; KUROIWA, Kentaro ; SONG, Yoohyun ; SUGIMOTO, Masaaki ; NAITO, Seiji ; ODA, Yoshinao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-ca454f3fcf95b31228ada20bc2f1ad0f92c40a02184cb09a51fef04a66950b0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Biological and medical sciences</topic><topic>Carcinogenesis</topic><topic>Cell Proliferation</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>MAP Kinase Signaling System - genetics</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Phosphorylation</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>raf Kinases - genetics</topic><topic>Signal Transduction</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><topic>Y-Box-Binding Protein 1 - genetics</topic><topic>Y-Box-Binding Protein 1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>IMADA, Kenjiro</creatorcontrib><creatorcontrib>SHIOTA, Masaki</creatorcontrib><creatorcontrib>KOHASHI, Kenichi</creatorcontrib><creatorcontrib>KUROIWA, Kentaro</creatorcontrib><creatorcontrib>SONG, Yoohyun</creatorcontrib><creatorcontrib>SUGIMOTO, Masaaki</creatorcontrib><creatorcontrib>NAITO, Seiji</creatorcontrib><creatorcontrib>ODA, Yoshinao</creatorcontrib><collection>Pascal-Francis</collection><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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>IMADA, Kenjiro</au><au>SHIOTA, Masaki</au><au>KOHASHI, Kenichi</au><au>KUROIWA, Kentaro</au><au>SONG, Yoohyun</au><au>SUGIMOTO, Masaaki</au><au>NAITO, Seiji</au><au>ODA, Yoshinao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box―Binding Protein-1 Promotes Prostate Cancer Progression</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>19</volume><issue>17</issue><spage>4638</spage><epage>4650</epage><pages>4638-4650</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>Y-box-binding protein-1 (YB-1) is known to conduct various functions related to cell proliferation, anti-apoptosis, epithelial-mesenchymal transition, and castration resistance in prostate cancer. However, it is still unknown how YB-1 affects cancer biology, especially its correlations with the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, we aimed to examine the interaction between YB-1 and the MAPK pathway in prostate cancer.
Quantitative real-time PCR, Western blotting, and co-immunoprecipitation assay were conducted in prostate cancer cells. YB-1, phosphorylated YB-1 (p-YB-1), and ERK2 protein expressions in 165 clinical specimens of prostate cancer were investigated by immunohistochemistry. YB-1, p-YB-1, and ERK2 nuclear expressions were compared with clinicopathologic characteristics and patient prognoses.
EGF upregulated p-YB-1, whereas MEK inhibitor (U0126, PD98059) decreased p-YB-1. Inversely, silencing of YB-1 using siRNA decreased the expression of ERK2 and phosphorylated MEK, ERK1/2, and RSK. Furthermore, YB-1 interacted with ERK2 and Raf-1 and regulated their expressions, through the proteasomal pathway. Immunohistochemical staining showed a significant correlation among the nuclear expressions of YB-1, p-YB-1, and ERK2. The Cox proportional hazards model revealed that high ERK2 expression was an independent prognostic factor [HR, 7.947; 95% confidence interval (CI), 3.527-20.508; P<0.0001].
We revealed the functional relationship between YB-1 and MAPK signaling and its biochemical relevance to the progression of prostate cancer. In addition, ERK2 expression was an independent prognostic factor. These findings suggest that both the ERK pathway and YB-1 may be promising molecular targets for prostate cancer diagnosis and therapeutics.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>23838318</pmid><doi>10.1158/1078-0432.CCR-12-3705</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Biological and medical sciences Carcinogenesis Cell Proliferation Epithelial-Mesenchymal Transition Gene Expression Regulation, Neoplastic Gynecology. Andrology. Obstetrics Humans Male Male genital diseases MAP Kinase Signaling System - genetics Medical sciences Nephrology. Urinary tract diseases Phosphorylation Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology raf Kinases - genetics Signal Transduction Tumors Tumors of the urinary system Urinary tract. Prostate gland Y-Box-Binding Protein 1 - genetics Y-Box-Binding Protein 1 - metabolism |
| title | Mutual Regulation between Raf/MEK/ERK Signaling and Y-Box―Binding Protein-1 Promotes Prostate Cancer Progression |
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