Oncotarget

Research Papers:

XAF1 promotes neuroblastoma tumor suppression and is required for KIF1Bβ-mediated apoptosis

Zhang'e Choo _, Rachel Yu Lin Koh, Karin Wallis, Timothy Jia Wei Koh, Chik Hong Kuick, Veronica Sobrado, Rajappa S. Kenchappa, Amos Hong Pheng Loh, Shui Yen Soh, Susanne Schlisio, Kenneth Tou En Chang, Zhi Xiong Chen

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Oncotarget. 2016; 7:34229-34239. https://doi.org/10.18632/oncotarget.8748

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Abstract

Zhang’e Choo1, Rachel Yu Lin Koh1, Karin Wallis2, Timothy Jia Wei Koh3, Chik Hong Kuick4, Veronica Sobrado2, Rajappa S. Kenchappa5, Amos Hong Pheng Loh6, Shui Yen Soh7, Susanne Schlisio2,8, Kenneth Tou En Chang4, Zhi Xiong Chen1

1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, S117597, Singapore, Singapore

2Ludwig Cancer Research (Stockholm), Karolinska Institutet, SE-17177, Stockholm, Sweden

3School of Life Sciences and Technology, Ngee Ann Polytechnic, S599489, Singapore, Singapore

4Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, S299899, Singapore

5Neuro-Oncology Program, Moffitt Cancer Center, Tampa, FL 33612, USA

6Department of Paediatric Surgery, KK Women’s and Children’s Hospital, S299899, Singapore, Singapore

7Department of Paediatric Hematology/Oncology, KK Women’s and Children’s Hospital, S299899, Singapore, Singapore

8Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden

Correspondence to:

Zhi Xiong Chen, email: zhixiong_chen@nuhs.edu.sg

Keywords: XAF1, neuroblastoma, KIF1Bβ, apoptosis

Received: August 13, 2015    Accepted: March 28, 2016    Published: April 15, 2016

ABSTRACT

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.

Author Information

Zhang'e Choo
Primary Contact  _

Rachel Yu Lin Koh

Karin Wallis

Timothy Jia Wei Koh

Chik Hong Kuick

Veronica Sobrado

Rajappa S. Kenchappa

Amos Hong Pheng Loh

Shui Yen Soh

Susanne Schlisio

Kenneth Tou En Chang

Zhi Xiong Chen


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