Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines
The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid...
Gespeichert in:
| Veröffentlicht in: | PloS one 2016-01, Vol.11 (1), p.e0147343-e0147343 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0147343 |
|---|---|
| container_issue | 1 |
| container_start_page | e0147343 |
| container_title | PloS one |
| container_volume | 11 |
| creator | Choi, Yeo-Jin Baek, Ga-Young Park, Hae-Ran Jo, Sung-Kee Jung, Uhee |
| description | The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines. |
| doi_str_mv | 10.1371/journal.pone.0147343 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1759161316</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A440892442</galeid><doaj_id>oai_doaj_org_article_7fb54a6df5cb42f9b0e767f4d61829df</doaj_id><sourcerecordid>A440892442</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-ef4f57b5a9ac4148574e644ed2705e3c65d7e8860b603f7808c7a8e2ab5913073</originalsourceid><addsrcrecordid>eNqNk89u1DAQxiMEoqXwBggiISE4ZOt_sZML0rItdKWtKrUFcbMcZ7LryrGXOIH2pXhGnO226qIeUA5OZn7fN_HYkySvMZpgKvDhlR86p-xk7R1MEGaCMvok2cclJRkniD598L6XvAjhCqGcFpw_T_YIF2XM4f3kz0WranJIs3NYDlb1UKfH1-sOQjDepb5JjxY_SDoP6TQEr80G-G36VXqu6vgVoWzu6kGPunWMgzXKZqcQwOnVTatsetkpF8xIpsrVG52P_ib0ymkYS0xzVm5yp0fT7PRzRihOT4ZWuXQ2Il06A2vThXEQXibPGmUDvNquB8m3L8eXs5NscfZ1PpsuMs1L0mfQsCYXVa5KpRlmRS4YcMagJgLlQDXPawFFwVHFEW1EgQotVAFEVXmJKRL0IHl767u2Pshtq4PEIuY5pphHYn5L1F5dyXVnWtXdSK-M3AR8t5Sq6422IEVT5Uzxusl1xUhTVggEFw2rOS5IWTfR69O22lC1UGtwfafsjuluxpmVXPpfkglCCc-jwYetQed_DhB62ZqgY9eUAz-M_81RiXC5Qd_9gz6-uy21VHEDxjU-1tWjqZwyhoqSMEYiNXmEik8NrdHxXjYmxncEH3cEkenhul-qIQQ5vzj_f_bs-y77_gG7AmX7VfB2GG9d2AXZLag7H0IHzX2TMZLjWN11Q45jJbdjFWVvHh7Qvehujuhf2kQbyQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1759161316</pqid></control><display><type>article</type><title>Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Choi, Yeo-Jin ; Baek, Ga-Young ; Park, Hae-Ran ; Jo, Sung-Kee ; Jung, Uhee</creator><contributor>Ahmad, Aamir</contributor><creatorcontrib>Choi, Yeo-Jin ; Baek, Ga-Young ; Park, Hae-Ran ; Jo, Sung-Kee ; Jung, Uhee ; Ahmad, Aamir</creatorcontrib><description>The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0147343</identifier><identifier>PMID: 26799321</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and life sciences ; Biomarkers ; Biotechnology ; Blood cancer ; Bone morphogenetic proteins ; Breast cancer ; Cancer ; Cell Line, Tumor ; Cell Movement - radiation effects ; Cell Survival - genetics ; Cell Survival - radiation effects ; Depletion ; Deregulation ; Epithelial-Mesenchymal Transition - radiation effects ; Gangrene ; Gene expression ; Growth factors ; Homeobox ; Homeodomain Proteins - biosynthesis ; Homeodomain Proteins - genetics ; Humans ; Hyaluronan Receptors - biosynthesis ; Immunoglobulins ; Invasiveness ; Ionizing radiation ; Irradiation ; Lung cancer ; Medicine and Health Sciences ; Mesenchyme ; Metabolism ; Metastases ; Metastasis ; Morphogenesis ; Neoplasm Invasiveness - pathology ; Neoplasms - pathology ; Neoplasms - radiotherapy ; Neoplastic Stem Cells - pathology ; Phosphorylation ; R&D ; Radiation ; Radiation effects ; Radiation therapy ; Radiation Tolerance - genetics ; Radioisotopes ; Radioresistance ; Research & development ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; RNA Interference ; RNA, Small Interfering - genetics ; Signal Transduction ; Signaling ; Smad2 protein ; Smad2 Protein - genetics ; Smad2 Protein - metabolism ; Smad3 Protein - genetics ; Smad3 Protein - metabolism ; Solid tumors ; Stem cells ; Transcription factors ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Transforming Growth Factor beta1 - metabolism ; Transforming growth factor-b1 ; Transforming growth factors ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2016-01, Vol.11 (1), p.e0147343-e0147343</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Choi et al 2016 Choi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ef4f57b5a9ac4148574e644ed2705e3c65d7e8860b603f7808c7a8e2ab5913073</citedby><cites>FETCH-LOGICAL-c692t-ef4f57b5a9ac4148574e644ed2705e3c65d7e8860b603f7808c7a8e2ab5913073</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/PMC4723265/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723265/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26799321$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ahmad, Aamir</contributor><creatorcontrib>Choi, Yeo-Jin</creatorcontrib><creatorcontrib>Baek, Ga-Young</creatorcontrib><creatorcontrib>Park, Hae-Ran</creatorcontrib><creatorcontrib>Jo, Sung-Kee</creatorcontrib><creatorcontrib>Jung, Uhee</creatorcontrib><title>Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines.</description><subject>Biology and life sciences</subject><subject>Biomarkers</subject><subject>Biotechnology</subject><subject>Blood cancer</subject><subject>Bone morphogenetic proteins</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - radiation effects</subject><subject>Cell Survival - genetics</subject><subject>Cell Survival - radiation effects</subject><subject>Depletion</subject><subject>Deregulation</subject><subject>Epithelial-Mesenchymal Transition - radiation effects</subject><subject>Gangrene</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - biosynthesis</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humans</subject><subject>Hyaluronan Receptors - biosynthesis</subject><subject>Immunoglobulins</subject><subject>Invasiveness</subject><subject>Ionizing radiation</subject><subject>Irradiation</subject><subject>Lung cancer</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchyme</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Morphogenesis</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - radiotherapy</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Phosphorylation</subject><subject>R&D</subject><subject>Radiation</subject><subject>Radiation effects</subject><subject>Radiation therapy</subject><subject>Radiation Tolerance - genetics</subject><subject>Radioisotopes</subject><subject>Radioresistance</subject><subject>Research & development</subject><subject>Research and Analysis Methods</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Smad2 protein</subject><subject>Smad2 Protein - genetics</subject><subject>Smad2 Protein - metabolism</subject><subject>Smad3 Protein - genetics</subject><subject>Smad3 Protein - metabolism</subject><subject>Solid tumors</subject><subject>Stem cells</subject><subject>Transcription factors</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Transforming growth factor-b1</subject><subject>Transforming growth factors</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk89u1DAQxiMEoqXwBggiISE4ZOt_sZML0rItdKWtKrUFcbMcZ7LryrGXOIH2pXhGnO226qIeUA5OZn7fN_HYkySvMZpgKvDhlR86p-xk7R1MEGaCMvok2cclJRkniD598L6XvAjhCqGcFpw_T_YIF2XM4f3kz0WranJIs3NYDlb1UKfH1-sOQjDepb5JjxY_SDoP6TQEr80G-G36VXqu6vgVoWzu6kGPunWMgzXKZqcQwOnVTatsetkpF8xIpsrVG52P_ib0ymkYS0xzVm5yp0fT7PRzRihOT4ZWuXQ2Il06A2vThXEQXibPGmUDvNquB8m3L8eXs5NscfZ1PpsuMs1L0mfQsCYXVa5KpRlmRS4YcMagJgLlQDXPawFFwVHFEW1EgQotVAFEVXmJKRL0IHl767u2Pshtq4PEIuY5pphHYn5L1F5dyXVnWtXdSK-M3AR8t5Sq6422IEVT5Uzxusl1xUhTVggEFw2rOS5IWTfR69O22lC1UGtwfafsjuluxpmVXPpfkglCCc-jwYetQed_DhB62ZqgY9eUAz-M_81RiXC5Qd_9gz6-uy21VHEDxjU-1tWjqZwyhoqSMEYiNXmEik8NrdHxXjYmxncEH3cEkenhul-qIQQ5vzj_f_bs-y77_gG7AmX7VfB2GG9d2AXZLag7H0IHzX2TMZLjWN11Q45jJbdjFWVvHh7Qvehujuhf2kQbyQ</recordid><startdate>20160122</startdate><enddate>20160122</enddate><creator>Choi, Yeo-Jin</creator><creator>Baek, Ga-Young</creator><creator>Park, Hae-Ran</creator><creator>Jo, Sung-Kee</creator><creator>Jung, Uhee</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160122</creationdate><title>Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines</title><author>Choi, Yeo-Jin ; Baek, Ga-Young ; Park, Hae-Ran ; Jo, Sung-Kee ; Jung, Uhee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ef4f57b5a9ac4148574e644ed2705e3c65d7e8860b603f7808c7a8e2ab5913073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Biology and life sciences</topic><topic>Biomarkers</topic><topic>Biotechnology</topic><topic>Blood cancer</topic><topic>Bone morphogenetic proteins</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - radiation effects</topic><topic>Cell Survival - genetics</topic><topic>Cell Survival - radiation effects</topic><topic>Depletion</topic><topic>Deregulation</topic><topic>Epithelial-Mesenchymal Transition - radiation effects</topic><topic>Gangrene</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Homeobox</topic><topic>Homeodomain Proteins - biosynthesis</topic><topic>Homeodomain Proteins - genetics</topic><topic>Humans</topic><topic>Hyaluronan Receptors - biosynthesis</topic><topic>Immunoglobulins</topic><topic>Invasiveness</topic><topic>Ionizing radiation</topic><topic>Irradiation</topic><topic>Lung cancer</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchyme</topic><topic>Metabolism</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Morphogenesis</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>Neoplasms - pathology</topic><topic>Neoplasms - radiotherapy</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Phosphorylation</topic><topic>R&D</topic><topic>Radiation</topic><topic>Radiation effects</topic><topic>Radiation therapy</topic><topic>Radiation Tolerance - genetics</topic><topic>Radioisotopes</topic><topic>Radioresistance</topic><topic>Research & development</topic><topic>Research and Analysis Methods</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Smad2 protein</topic><topic>Smad2 Protein - genetics</topic><topic>Smad2 Protein - metabolism</topic><topic>Smad3 Protein - genetics</topic><topic>Smad3 Protein - metabolism</topic><topic>Solid tumors</topic><topic>Stem cells</topic><topic>Transcription factors</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Transforming growth factor-b1</topic><topic>Transforming growth factors</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Yeo-Jin</creatorcontrib><creatorcontrib>Baek, Ga-Young</creatorcontrib><creatorcontrib>Park, Hae-Ran</creatorcontrib><creatorcontrib>Jo, Sung-Kee</creatorcontrib><creatorcontrib>Jung, Uhee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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 China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Yeo-Jin</au><au>Baek, Ga-Young</au><au>Park, Hae-Ran</au><au>Jo, Sung-Kee</au><au>Jung, Uhee</au><au>Ahmad, Aamir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-01-22</date><risdate>2016</risdate><volume>11</volume><issue>1</issue><spage>e0147343</spage><epage>e0147343</epage><pages>e0147343-e0147343</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26799321</pmid><doi>10.1371/journal.pone.0147343</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-01, Vol.11 (1), p.e0147343-e0147343 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1759161316 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Biology and life sciences Biomarkers Biotechnology Blood cancer Bone morphogenetic proteins Breast cancer Cancer Cell Line, Tumor Cell Movement - radiation effects Cell Survival - genetics Cell Survival - radiation effects Depletion Deregulation Epithelial-Mesenchymal Transition - radiation effects Gangrene Gene expression Growth factors Homeobox Homeodomain Proteins - biosynthesis Homeodomain Proteins - genetics Humans Hyaluronan Receptors - biosynthesis Immunoglobulins Invasiveness Ionizing radiation Irradiation Lung cancer Medicine and Health Sciences Mesenchyme Metabolism Metastases Metastasis Morphogenesis Neoplasm Invasiveness - pathology Neoplasms - pathology Neoplasms - radiotherapy Neoplastic Stem Cells - pathology Phosphorylation R&D Radiation Radiation effects Radiation therapy Radiation Tolerance - genetics Radioisotopes Radioresistance Research & development Research and Analysis Methods Ribonucleic acid RNA RNA Interference RNA, Small Interfering - genetics Signal Transduction Signaling Smad2 protein Smad2 Protein - genetics Smad2 Protein - metabolism Smad3 Protein - genetics Smad3 Protein - metabolism Solid tumors Stem cells Transcription factors Transcription Factors - biosynthesis Transcription Factors - genetics Transforming Growth Factor beta1 - metabolism Transforming growth factor-b1 Transforming growth factors Tumor cell lines Tumors |
| title | Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T17%3A19%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Smad2/3-Regulated%20Expression%20of%20DLX2%20Is%20Associated%20with%20Radiation-Induced%20Epithelial-Mesenchymal%20Transition%20and%20Radioresistance%20of%20A549%20and%20MDA-MB-231%20Human%20Cancer%20Cell%20Lines&rft.jtitle=PloS%20one&rft.au=Choi,%20Yeo-Jin&rft.date=2016-01-22&rft.volume=11&rft.issue=1&rft.spage=e0147343&rft.epage=e0147343&rft.pages=e0147343-e0147343&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0147343&rft_dat=%3Cgale_plos_%3EA440892442%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1759161316&rft_id=info:pmid/26799321&rft_galeid=A440892442&rft_doaj_id=oai_doaj_org_article_7fb54a6df5cb42f9b0e767f4d61829df&rfr_iscdi=true |