XAF1 promotes neuroblastoma tumor suppression and is required for KIF1Bβ-mediated apoptosis
| Autor: | Amos Hong Pheng Loh, Timothy Jia Wei Koh, Zhang'e Choo, Veronica Sobrado, Susanne Schlisio, Karin Wallis, Rajappa S. Kenchappa, Rachel Yu Lin Koh, Zhi Xiong Chen, Shui Yen Soh, Chik Hong Kuick, Kenneth Tou En Chang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gerontology Gene isoform Kinesins Kaplan-Meier Estimate law.invention Mice Neuroblastoma 03 medical and health sciences law Cell Line Tumor Biomarkers Tumor Animals Humans Medicine Gene silencing Adaptor Proteins Signal Transducing Mice Knockout Gene knockdown business.industry F-Box Proteins Tumor Suppressor Proteins XAF1 apoptosis Intracellular Signaling Peptides and Proteins Prognosis medicine.disease Neoplasm Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Tumor progression Apoptosis Cancer research Heterografts Suppressor Kinesin KIF1Bβ Apoptosis Regulatory Proteins business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Neuroblastoma is an aggressive, relapse-prone childhood tumor of the sympathetic nervous system. Current treatment modalities do not fully exploit the genetic basis between the different molecular subtypes and little is known about the targets discovered in recent mutational and genetic studies. Neuroblastomas with poor prognosis are often characterized by 1p36 deletion, containing the kinesin gene KIF1B. Its beta isoform, KIF1Bβ, is required for NGF withdrawal-dependent apoptosis, mediated by the induction of XIAP-associated Factor 1 (XAF1). Here, we showed that XAF1 low expression correlates with poor survival and disease status. KIF1Bβ deletion results in loss of XAF1 expression, suggesting that XAF1 is indeed a downstream target of KIF1Bβ. XAF1 silencing protects from NGF withdrawal and from KIF1Bβ-mediated apoptosis. Overexpression of XAF1 impairs tumor progression whereas knockdown of XAF1 promotes tumor growth, suggesting that XAF1 may be a candidate tumor suppressor in neuroblastoma and its associated pathway may be important for developing future interventions. |
| Databáze: | OpenAIRE |
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