STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer
The importance of store-operated Ca 2+ entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2015-08, Vol.5 (1), p.11754-11754, Article 11754 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 11754 |
|---|---|
| container_issue | 1 |
| container_start_page | 11754 |
| container_title | Scientific reports |
| container_volume | 5 |
| creator | Xu, Yingxi Zhang, Shu Niu, Haiying Ye, Yujie Hu, Fen Chen, Si Li, Xuefei Luo, Xiaohe Jiang, Shan Liu, Yanhua Chen, Yanan Li, Junying Xiang, Rong Li, Na |
| description | The importance of store-operated Ca
2+
entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human hyperplasia and tumor tissues of high histological grade and by demonstrating that STIM1 and ORAI1 inhibit cell growth by arresting the G0/G1 phase and enhancing cell senescence in human prostate cancer cells. In addition, STIM1 and ORAI1 inhibited NF-κB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development. However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-β, Snail and Wnt/β-Catenin pathways. Thus, our study revealed novel regulatory effects and the mechanisms by which STIM1 affects cell senescence, tumor migration and the tumor microenvironment, revealing that STIM1 has multiple functions in prostate cancer cells. |
| doi_str_mv | 10.1038/srep11754 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4530453</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899718541</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-e9a0fdbf7fb28ac14ee7e3b063ae739f706756f7176e3f49a62d0a8f1943ebaa3</originalsourceid><addsrcrecordid>eNplkctq3TAQhk1paUKSRV-gCLppC050s2VvCiX0EkjJoulayPIoR8GWXEkO5BX61J3DSQ-nrTYzMJ_-ufxV9YrRc0ZFd5ETLIypRj6rjjmVTc0F588P8qPqLOd7iq_hvWT9y-qIt7xRVLXH1a_vt1ffGDHWwgTJFMgEs4lkCJAtBAvEB2JIgjmOiIxk9jZFCA8-xTBDKGRYC4GwMchmUjZAYPEYJm-musR6BtSym8fZTKQkE7IvPoat6pJiLtiS2O3fdFq9cGbKcPYUT6ofnz_dXn6tr2--XF1-vK6tFF2poTfUjYNTbuCdsUwCKBADbYUBJXqnaKua1immWhBO9qblIzWdY70UMBgjTqoPO91lHWYYcUkca9JL8rNJjzoar_-uBL_Rd_FBy0bgTQUKvH0SSPHnCrno2eft1UyAuGbNFBVcStVTRN_8g97HNQVcT7Ou7xXrGsmQerej8LIZ_XT7YRjVW5P13mRkXx9Ovyf_WIrA-x2QsRTuIB20_E_tN-07tLc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899718541</pqid></control><display><type>article</type><title>STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Xu, Yingxi ; Zhang, Shu ; Niu, Haiying ; Ye, Yujie ; Hu, Fen ; Chen, Si ; Li, Xuefei ; Luo, Xiaohe ; Jiang, Shan ; Liu, Yanhua ; Chen, Yanan ; Li, Junying ; Xiang, Rong ; Li, Na</creator><creatorcontrib>Xu, Yingxi ; Zhang, Shu ; Niu, Haiying ; Ye, Yujie ; Hu, Fen ; Chen, Si ; Li, Xuefei ; Luo, Xiaohe ; Jiang, Shan ; Liu, Yanhua ; Chen, Yanan ; Li, Junying ; Xiang, Rong ; Li, Na</creatorcontrib><description>The importance of store-operated Ca
2+
entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human hyperplasia and tumor tissues of high histological grade and by demonstrating that STIM1 and ORAI1 inhibit cell growth by arresting the G0/G1 phase and enhancing cell senescence in human prostate cancer cells. In addition, STIM1 and ORAI1 inhibited NF-κB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development. However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-β, Snail and Wnt/β-Catenin pathways. Thus, our study revealed novel regulatory effects and the mechanisms by which STIM1 affects cell senescence, tumor migration and the tumor microenvironment, revealing that STIM1 has multiple functions in prostate cancer cells.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep11754</identifier><identifier>PMID: 26257076</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/105 ; 13/2 ; 13/21 ; 13/95 ; 14 ; 14/35 ; 631/67/2329 ; 631/67/327 ; 631/67/581 ; 631/67/589/466 ; 82/79 ; 96 ; Androgens ; Animals ; beta Catenin - metabolism ; Calcium channels ; Calcium Channels - genetics ; Calcium Channels - metabolism ; Calcium influx ; Cell adhesion & migration ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cellular Senescence ; Down-Regulation ; Epithelial-Mesenchymal Transition ; G1 phase ; G1 Phase Cell Cycle Checkpoints ; Humanities and Social Sciences ; Humans ; Hyperplasia ; Leukocyte migration ; Macrophages ; Macrophages - cytology ; Macrophages - immunology ; Male ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mesenchyme ; Mice ; Mice, Inbred NOD ; Mice, SCID ; multidisciplinary ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; NF-kappa B - metabolism ; ORAI1 Protein ; Prostate cancer ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Science ; Senescence ; Signal Transduction ; Snail Family Transcription Factors ; STIM1 protein ; Stromal Interaction Molecule 1 ; Transcription Factors - metabolism ; Transforming Growth Factor beta - metabolism ; Transplantation, Heterologous ; Tumor Microenvironment ; Wnt protein ; Wnt Proteins - metabolism ; β-Catenin</subject><ispartof>Scientific reports, 2015-08, Vol.5 (1), p.11754-11754, Article 11754</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Aug 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-e9a0fdbf7fb28ac14ee7e3b063ae739f706756f7176e3f49a62d0a8f1943ebaa3</citedby><cites>FETCH-LOGICAL-c438t-e9a0fdbf7fb28ac14ee7e3b063ae739f706756f7176e3f49a62d0a8f1943ebaa3</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/PMC4530453/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530453/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26257076$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Yingxi</creatorcontrib><creatorcontrib>Zhang, Shu</creatorcontrib><creatorcontrib>Niu, Haiying</creatorcontrib><creatorcontrib>Ye, Yujie</creatorcontrib><creatorcontrib>Hu, Fen</creatorcontrib><creatorcontrib>Chen, Si</creatorcontrib><creatorcontrib>Li, Xuefei</creatorcontrib><creatorcontrib>Luo, Xiaohe</creatorcontrib><creatorcontrib>Jiang, Shan</creatorcontrib><creatorcontrib>Liu, Yanhua</creatorcontrib><creatorcontrib>Chen, Yanan</creatorcontrib><creatorcontrib>Li, Junying</creatorcontrib><creatorcontrib>Xiang, Rong</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><title>STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The importance of store-operated Ca
2+
entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human hyperplasia and tumor tissues of high histological grade and by demonstrating that STIM1 and ORAI1 inhibit cell growth by arresting the G0/G1 phase and enhancing cell senescence in human prostate cancer cells. In addition, STIM1 and ORAI1 inhibited NF-κB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development. However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-β, Snail and Wnt/β-Catenin pathways. Thus, our study revealed novel regulatory effects and the mechanisms by which STIM1 affects cell senescence, tumor migration and the tumor microenvironment, revealing that STIM1 has multiple functions in prostate cancer cells.</description><subject>13/1</subject><subject>13/105</subject><subject>13/2</subject><subject>13/21</subject><subject>13/95</subject><subject>14</subject><subject>14/35</subject><subject>631/67/2329</subject><subject>631/67/327</subject><subject>631/67/581</subject><subject>631/67/589/466</subject><subject>82/79</subject><subject>96</subject><subject>Androgens</subject><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Calcium channels</subject><subject>Calcium Channels - genetics</subject><subject>Calcium Channels - metabolism</subject><subject>Calcium influx</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cellular Senescence</subject><subject>Down-Regulation</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>G1 phase</subject><subject>G1 Phase Cell Cycle Checkpoints</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>Leukocyte migration</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>multidisciplinary</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>ORAI1 Protein</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Science</subject><subject>Senescence</subject><subject>Signal Transduction</subject><subject>Snail Family Transcription Factors</subject><subject>STIM1 protein</subject><subject>Stromal Interaction Molecule 1</subject><subject>Transcription Factors - metabolism</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Transplantation, Heterologous</subject><subject>Tumor Microenvironment</subject><subject>Wnt protein</subject><subject>Wnt Proteins - metabolism</subject><subject>β-Catenin</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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>eNplkctq3TAQhk1paUKSRV-gCLppC050s2VvCiX0EkjJoulayPIoR8GWXEkO5BX61J3DSQ-nrTYzMJ_-ufxV9YrRc0ZFd5ETLIypRj6rjjmVTc0F588P8qPqLOd7iq_hvWT9y-qIt7xRVLXH1a_vt1ffGDHWwgTJFMgEs4lkCJAtBAvEB2JIgjmOiIxk9jZFCA8-xTBDKGRYC4GwMchmUjZAYPEYJm-musR6BtSym8fZTKQkE7IvPoat6pJiLtiS2O3fdFq9cGbKcPYUT6ofnz_dXn6tr2--XF1-vK6tFF2poTfUjYNTbuCdsUwCKBADbYUBJXqnaKua1immWhBO9qblIzWdY70UMBgjTqoPO91lHWYYcUkca9JL8rNJjzoar_-uBL_Rd_FBy0bgTQUKvH0SSPHnCrno2eft1UyAuGbNFBVcStVTRN_8g97HNQVcT7Ou7xXrGsmQerej8LIZ_XT7YRjVW5P13mRkXx9Ovyf_WIrA-x2QsRTuIB20_E_tN-07tLc</recordid><startdate>20150810</startdate><enddate>20150810</enddate><creator>Xu, Yingxi</creator><creator>Zhang, Shu</creator><creator>Niu, Haiying</creator><creator>Ye, Yujie</creator><creator>Hu, Fen</creator><creator>Chen, Si</creator><creator>Li, Xuefei</creator><creator>Luo, Xiaohe</creator><creator>Jiang, Shan</creator><creator>Liu, Yanhua</creator><creator>Chen, Yanan</creator><creator>Li, Junying</creator><creator>Xiang, Rong</creator><creator>Li, Na</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>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>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>20150810</creationdate><title>STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer</title><author>Xu, Yingxi ; Zhang, Shu ; Niu, Haiying ; Ye, Yujie ; Hu, Fen ; Chen, Si ; Li, Xuefei ; Luo, Xiaohe ; Jiang, Shan ; Liu, Yanhua ; Chen, Yanan ; Li, Junying ; Xiang, Rong ; Li, Na</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-e9a0fdbf7fb28ac14ee7e3b063ae739f706756f7176e3f49a62d0a8f1943ebaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>13/1</topic><topic>13/105</topic><topic>13/2</topic><topic>13/21</topic><topic>13/95</topic><topic>14</topic><topic>14/35</topic><topic>631/67/2329</topic><topic>631/67/327</topic><topic>631/67/581</topic><topic>631/67/589/466</topic><topic>82/79</topic><topic>96</topic><topic>Androgens</topic><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>Calcium channels</topic><topic>Calcium Channels - genetics</topic><topic>Calcium Channels - metabolism</topic><topic>Calcium influx</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cellular Senescence</topic><topic>Down-Regulation</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>G1 phase</topic><topic>G1 Phase Cell Cycle Checkpoints</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hyperplasia</topic><topic>Leukocyte migration</topic><topic>Macrophages</topic><topic>Macrophages - cytology</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>multidisciplinary</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>ORAI1 Protein</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Science</topic><topic>Senescence</topic><topic>Signal Transduction</topic><topic>Snail Family Transcription Factors</topic><topic>STIM1 protein</topic><topic>Stromal Interaction Molecule 1</topic><topic>Transcription Factors - metabolism</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Transplantation, Heterologous</topic><topic>Tumor Microenvironment</topic><topic>Wnt protein</topic><topic>Wnt Proteins - metabolism</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Yingxi</creatorcontrib><creatorcontrib>Zhang, Shu</creatorcontrib><creatorcontrib>Niu, Haiying</creatorcontrib><creatorcontrib>Ye, Yujie</creatorcontrib><creatorcontrib>Hu, Fen</creatorcontrib><creatorcontrib>Chen, Si</creatorcontrib><creatorcontrib>Li, Xuefei</creatorcontrib><creatorcontrib>Luo, Xiaohe</creatorcontrib><creatorcontrib>Jiang, Shan</creatorcontrib><creatorcontrib>Liu, Yanhua</creatorcontrib><creatorcontrib>Chen, Yanan</creatorcontrib><creatorcontrib>Li, Junying</creatorcontrib><creatorcontrib>Xiang, Rong</creatorcontrib><creatorcontrib>Li, Na</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>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 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>Access via ProQuest (Open Access)</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>Xu, Yingxi</au><au>Zhang, Shu</au><au>Niu, Haiying</au><au>Ye, Yujie</au><au>Hu, Fen</au><au>Chen, Si</au><au>Li, Xuefei</au><au>Luo, Xiaohe</au><au>Jiang, Shan</au><au>Liu, Yanhua</au><au>Chen, Yanan</au><au>Li, Junying</au><au>Xiang, Rong</au><au>Li, Na</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-08-10</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>11754</spage><epage>11754</epage><pages>11754-11754</pages><artnum>11754</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The importance of store-operated Ca
2+
entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human hyperplasia and tumor tissues of high histological grade and by demonstrating that STIM1 and ORAI1 inhibit cell growth by arresting the G0/G1 phase and enhancing cell senescence in human prostate cancer cells. In addition, STIM1 and ORAI1 inhibited NF-κB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development. However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-β, Snail and Wnt/β-Catenin pathways. Thus, our study revealed novel regulatory effects and the mechanisms by which STIM1 affects cell senescence, tumor migration and the tumor microenvironment, revealing that STIM1 has multiple functions in prostate cancer cells.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26257076</pmid><doi>10.1038/srep11754</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2015-08, Vol.5 (1), p.11754-11754, Article 11754 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4530453 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 13/1 13/105 13/2 13/21 13/95 14 14/35 631/67/2329 631/67/327 631/67/581 631/67/589/466 82/79 96 Androgens Animals beta Catenin - metabolism Calcium channels Calcium Channels - genetics Calcium Channels - metabolism Calcium influx Cell adhesion & migration Cell Line, Tumor Cell Movement Cell Proliferation Cellular Senescence Down-Regulation Epithelial-Mesenchymal Transition G1 phase G1 Phase Cell Cycle Checkpoints Humanities and Social Sciences Humans Hyperplasia Leukocyte migration Macrophages Macrophages - cytology Macrophages - immunology Male Membrane Proteins - genetics Membrane Proteins - metabolism Mesenchyme Mice Mice, Inbred NOD Mice, SCID multidisciplinary Neoplasm Proteins - genetics Neoplasm Proteins - metabolism NF-kappa B - metabolism ORAI1 Protein Prostate cancer Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Science Senescence Signal Transduction Snail Family Transcription Factors STIM1 protein Stromal Interaction Molecule 1 Transcription Factors - metabolism Transforming Growth Factor beta - metabolism Transplantation, Heterologous Tumor Microenvironment Wnt protein Wnt Proteins - metabolism β-Catenin |
| title | STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T21%3A00%3A01IST&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=STIM1%20accelerates%20cell%20senescence%20in%20a%20remodeled%20microenvironment%20but%20enhances%20the%20epithelial-to-mesenchymal%20transition%20in%20prostate%20cancer&rft.jtitle=Scientific%20reports&rft.au=Xu,%20Yingxi&rft.date=2015-08-10&rft.volume=5&rft.issue=1&rft.spage=11754&rft.epage=11754&rft.pages=11754-11754&rft.artnum=11754&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep11754&rft_dat=%3Cproquest_pubme%3E1899718541%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=1899718541&rft_id=info:pmid/26257076&rfr_iscdi=true |