Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer
Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic s...
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| Veröffentlicht in: | International journal of oncology 2015-04, Vol.46 (4), p.1844-1848 |
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| creator | TOGE, MASAYOSHI YOKOYAMA, SATORU KATO, SHINICHIRO SAKURAI, HIROAKI SENDA, KAZUTAKA DOKI, YOSHINORI HAYAKAWA, YOSHIHIRO YOSHIMURA, NAOKI SAIKI, IKUO |
| description | Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-β-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies. |
| doi_str_mv | 10.3892/ijo.2015.2861 |
| format | Article |
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Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-β-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2015.2861</identifier><identifier>PMID: 25647738</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Apoptosis ; Cancer ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Care and treatment ; Cell Line, Tumor ; chemo-resistance ; Chemotherapy ; Cisplatin - pharmacology ; Drug resistance ; Drug Resistance, Neoplasm ; Drugs ; Epithelial-Mesenchymal Transition ; epithelial-to-mesenchymal transition ; Gene expression ; Genetic aspects ; Genetic research ; Humans ; Lung cancer ; Lung cancer, Non-small cell ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; MCL-1 ; Metastasis ; Minor Histocompatibility Antigens ; Myeloid Cell Leukemia Sequence 1 Protein - genetics ; Myeloid Cell Leukemia Sequence 1 Protein - metabolism ; non-small cell lung cancer ; Oncology, Experimental ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; TGF-β ; Transforming Growth Factor beta - pharmacology</subject><ispartof>International journal of oncology, 2015-04, Vol.46 (4), p.1844-1848</ispartof><rights>Copyright © 2015, Spandidos Publications</rights><rights>COPYRIGHT 2015 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c600t-41b51b4680b7ae9ceb10396c316a0224ffbeec0e9980da0735a5de5bf02d7e6f3</citedby><cites>FETCH-LOGICAL-c600t-41b51b4680b7ae9ceb10396c316a0224ffbeec0e9980da0735a5de5bf02d7e6f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,5556,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25647738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TOGE, MASAYOSHI</creatorcontrib><creatorcontrib>YOKOYAMA, SATORU</creatorcontrib><creatorcontrib>KATO, SHINICHIRO</creatorcontrib><creatorcontrib>SAKURAI, HIROAKI</creatorcontrib><creatorcontrib>SENDA, KAZUTAKA</creatorcontrib><creatorcontrib>DOKI, YOSHINORI</creatorcontrib><creatorcontrib>HAYAKAWA, YOSHIHIRO</creatorcontrib><creatorcontrib>YOSHIMURA, NAOKI</creatorcontrib><creatorcontrib>SAIKI, IKUO</creatorcontrib><title>Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-β-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.</description><subject>Apoptosis</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>chemo-resistance</subject><subject>Chemotherapy</subject><subject>Cisplatin - pharmacology</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Drugs</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>epithelial-to-mesenchymal transition</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Humans</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>MCL-1</subject><subject>Metastasis</subject><subject>Minor Histocompatibility Antigens</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein - genetics</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein - metabolism</subject><subject>non-small cell lung cancer</subject><subject>Oncology, Experimental</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>TGF-β</subject><subject>Transforming Growth Factor beta - pharmacology</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpt0c-L1DAUB_AiiruuHr1KQdBTxpefbY7DsP6AWbys55CmrzsZ2mRM2sP-96bOuroggSSET17I-1bVWwob3mr2yR_jhgGVG9Yq-qy6pI2mhAnGn5c9UE2U4PqiepXzEYBJCfRldcGkEk3D28uq3yU_e2fH2sUwJ98ts4-hjkN9s9sTWvtQX9_cEptzdN7O2NfugFMkCbPPsw0OV7KVQtchBpInO5ZSWKZxCXe1W0V6Xb0Y7JjxzcN6Vf34fH27-0r237982233xCmAmQjaSdoJ1ULXWNQOOwpcK8epssCYGIYO0QFq3UJvoeHSyh5lNwDrG1QDv6ren-ueUvy5YJ7NMS4plCcN1Zxxprlu_qo7O6LxYYhzsm7y2ZmtAA2taviqNv9RZfQ4-dIrHHw5f3Lhwz8XDmjH-ZDj-Luf-SkkZ-hSzDnhYE7JTzbdGwpmzdSUTM2aqVkzLf7dw6-WbsL-Uf8JsYCPZ5BPNvS-j_nRlEpEKAKC0FYI_gtrBKZK</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>TOGE, MASAYOSHI</creator><creator>YOKOYAMA, SATORU</creator><creator>KATO, SHINICHIRO</creator><creator>SAKURAI, HIROAKI</creator><creator>SENDA, KAZUTAKA</creator><creator>DOKI, YOSHINORI</creator><creator>HAYAKAWA, YOSHIHIRO</creator><creator>YOSHIMURA, NAOKI</creator><creator>SAIKI, IKUO</creator><general>D.A. 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Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-β-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>25647738</pmid><doi>10.3892/ijo.2015.2861</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of oncology, 2015-04, Vol.46 (4), p.1844-1848 |
| issn | 1019-6439 1791-2423 |
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| source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Apoptosis Cancer Cancer therapies Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Care and treatment Cell Line, Tumor chemo-resistance Chemotherapy Cisplatin - pharmacology Drug resistance Drug Resistance, Neoplasm Drugs Epithelial-Mesenchymal Transition epithelial-to-mesenchymal transition Gene expression Genetic aspects Genetic research Humans Lung cancer Lung cancer, Non-small cell Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology MCL-1 Metastasis Minor Histocompatibility Antigens Myeloid Cell Leukemia Sequence 1 Protein - genetics Myeloid Cell Leukemia Sequence 1 Protein - metabolism non-small cell lung cancer Oncology, Experimental Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism TGF-β Transforming Growth Factor beta - pharmacology |
| title | Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer |
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