Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas
Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene exp...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-03-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00043/full |
| _version_ | 1818128519971995648 |
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| author | Ming-Fu eChiang Pei-Yi eChou Wan-Jen eWang Chun-I eSze Nan-Shan eChang Nan-Shan eChang Nan-Shan eChang Nan-Shan eChang |
| author_facet | Ming-Fu eChiang Pei-Yi eChou Wan-Jen eWang Chun-I eSze Nan-Shan eChang Nan-Shan eChang Nan-Shan eChang Nan-Shan eChang |
| author_sort | Ming-Fu eChiang |
| collection | DOAJ |
| description | Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and postulate a potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death. |
| first_indexed | 2024-12-11T07:34:33Z |
| format | Article |
| id | doaj.art-7473f666afa447958dac6e35565bc4d8 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T07:34:33Z |
| publishDate | 2013-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-7473f666afa447958dac6e35565bc4d82022-12-22T01:15:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2013-03-01310.3389/fonc.2013.0004341512Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomasMing-Fu eChiang0Pei-Yi eChou1Wan-Jen eWang2Chun-I eSze3Nan-Shan eChang4Nan-Shan eChang5Nan-Shan eChang6Nan-Shan eChang7Mackay Memorial HospitalNational Cheng Kung UniversityNational Cheng Kung UniversityNational Cheng Kung UniversityNational Cheng Kung UniversityNational Cheng Kung UniversitySUNY Upstate Medical UniversityNew York State Institute for Basic Research in Developmental DisabilitiesTumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and postulate a potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death.http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00043/fullp53tumor suppressorGlioblastoma MultiformeWWOXtemozolomide resistance |
| spellingShingle | Ming-Fu eChiang Pei-Yi eChou Wan-Jen eWang Chun-I eSze Nan-Shan eChang Nan-Shan eChang Nan-Shan eChang Nan-Shan eChang Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas Frontiers in Oncology p53 tumor suppressor Glioblastoma Multiforme WWOX temozolomide resistance |
| title | Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas |
| title_full | Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas |
| title_fullStr | Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas |
| title_full_unstemmed | Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas |
| title_short | Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas |
| title_sort | tumor suppressor wwox and p53 alterations and drug resistance in glioblastomas |
| topic | p53 tumor suppressor Glioblastoma Multiforme WWOX temozolomide resistance |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00043/full |
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