TY - JOUR
T1 - XAF1 promotes neuroblastoma tumor suppression and is required for KIF1Bβ-mediated apoptosis
AU - Choo, Zhang'e
AU - Koh, Rachel Yu Lin
AU - Wallis, Karin
AU - Koh, Timothy Jia Wei
AU - Kuick, Chik Hong
AU - Sobrado, Veronica
AU - Kenchappa, Rajappa S.
AU - Loh, Amos Hong Pheng
AU - Soh, Shui Yen
AU - Schlisio, Susanne
AU - Chang, Kenneth Tou En
AU - Chen, Zhi Xiong
PY - 2016/6/7
Y1 - 2016/6/7
N2 - 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.
AB - 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.
KW - Apoptosis
KW - KIF1Bβ
KW - Neuroblastoma
KW - XAF1
UR - http://www.scopus.com/inward/record.url?scp=84973661042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84973661042&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.8748
DO - 10.18632/oncotarget.8748
M3 - Article
C2 - 27097110
AN - SCOPUS:84973661042
SN - 1949-2553
VL - 7
SP - 34229
EP - 34239
JO - Oncotarget
JF - Oncotarget
IS - 23
ER -