DC Field | Value | Language |
---|---|---|
dc.contributor.author | Aldonza, Mark Borris D | ko |
dc.contributor.author | Hong, Ji-Young | ko |
dc.contributor.author | Alinsug, Malona V. | ko |
dc.contributor.author | Song, Jayoung | ko |
dc.contributor.author | Lee, Sang Kook | ko |
dc.date.accessioned | 2016-07-25T09:38:07Z | - |
dc.date.available | 2016-07-25T09:38:07Z | - |
dc.date.created | 2016-07-12 | - |
dc.date.created | 2016-07-12 | - |
dc.date.issued | 2016-06 | - |
dc.identifier.citation | ONCOTARGET, v.7, no.23, pp.34395 - 34419 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | http://hdl.handle.net/10203/212133 | - |
dc.description.abstract | Acquired drug resistance is a primary obstacle for effective cancer therapy. The correlation of point mutations in class III beta-tubulin (TUBB3) and the prominent overexpression of ATP-binding cassette P-glycoprotein (ABCB1), a multidrug resistance gene, have been protruding mechanisms of resistance to microtubule disruptors such as paclitaxel (PTX) for many cancers. However, the precise underlying mechanism of the rapid onset of cross-resistance to an array of structurally and functionally unrelated drugs in PTX-resistant cancers has been poorly understood. We determined that our established PTX-resistant cancer cells display ABCB1/ABCC1-associated cross-resistance to chemically different drugs such as 5-fluorouracil, docetaxel, and cisplatin. We found that feedback activation of TUBB3 can be triggered through the FOXO3a-dependent regulation of ABCB1, which resulted in the accentuation of induced PTX resistance and encouraged multiplicity in acquired cross-resistance. FOXO3a-directed regulation of P-glycoprotein (P-gp) function suggests that control of ABCB1 involves methylation-dependent activation. Consistently, transcriptional overexpression or downregulation of FOXO3a directs inhibitor-controlled protease-degradation of TUBB3. The functional PI3K/Akt signaling is tightly responsive to FOXO3a activation alongside doxorubicin treatment, which directs FOXO3a arginine hypermethylation. In addition, we found that secretome factors from PTX-resistant cancer cells with acquired cross-resistance support a P-gp-dependent association in multidrug resistance (MDR) development, which assisted the FOXO3a-mediated control of TUBB3 feedback. The direct silencing of TUBB3 reverses induced multiple cross-resistance, reduces drug-resistant tumor mass, and suppresses the impaired microtubule stability status of PTX-resistant cells with transient cross-resistance. These findings highlight the control of the TUBB3 response to ABCB1 genetic suppressors as a mechanism to reverse the profuse development of multidrug resistance in cancer | - |
dc.language | English | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.subject | III BETA-TUBULIN | - |
dc.subject | BREAST-CANCER | - |
dc.subject | MULTIDRUG-RESISTANCE | - |
dc.subject | DRUG-RESISTANCE | - |
dc.subject | LUNG-CANCER | - |
dc.subject | TUMOR MICROENVIRONMENT | - |
dc.subject | MEDIATED APOPTOSIS | - |
dc.subject | SIGNALING PATHWAY | - |
dc.subject | DNA METHYLATION | - |
dc.subject | PROSTATE-CANCER | - |
dc.title | Multiplicity of acquired cross-resistance in paclitaxel-resistant cancer cells is associated with feedback control of TUBB3 via FOXO3a-mediated ABCB1 regulation | - |
dc.type | Article | - |
dc.identifier.wosid | 000377752100067 | - |
dc.identifier.scopusid | 2-s2.0-84973659481 | - |
dc.type.rims | ART | - |
dc.citation.volume | 7 | - |
dc.citation.issue | 23 | - |
dc.citation.beginningpage | 34395 | - |
dc.citation.endingpage | 34419 | - |
dc.citation.publicationname | ONCOTARGET | - |
dc.identifier.doi | 10.18632/oncotarget.9118 | - |
dc.contributor.localauthor | Aldonza, Mark Borris D | - |
dc.contributor.nonIdAuthor | Hong, Ji-Young | - |
dc.contributor.nonIdAuthor | Alinsug, Malona V. | - |
dc.contributor.nonIdAuthor | Song, Jayoung | - |
dc.contributor.nonIdAuthor | Lee, Sang Kook | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | paclitaxel resistance | - |
dc.subject.keywordAuthor | multidrug resistance | - |
dc.subject.keywordAuthor | FOXO3a | - |
dc.subject.keywordAuthor | TUBB3 | - |
dc.subject.keywordAuthor | ABCB1 | - |
dc.subject.keywordPlus | III BETA-TUBULIN | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | MULTIDRUG-RESISTANCE | - |
dc.subject.keywordPlus | DRUG-RESISTANCE | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | TUMOR MICROENVIRONMENT | - |
dc.subject.keywordPlus | MEDIATED APOPTOSIS | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | DNA METHYLATION | - |
dc.subject.keywordPlus | PROSTATE-CANCER | - |
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