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Reactivating p53 functions by suppressing its novel inhibitor iASPP : a potential therapeutic opportunity in p53 wild-type tumors

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Title: Reactivating p53 functions by suppressing its novel inhibitor iASPP : a potential therapeutic opportunity in p53 wild-type tumors
Authors: Dong, Peixin Browse this author
Ihira, Kei Browse this author
Hamada, Junichi Browse this author
Watari, Hidemichi Browse this author →KAKEN DB
Yamada, Takahiro Browse this author →KAKEN DB
Hosaka, Masayoshi Browse this author
Hanley, Sharon J. B. Browse this author →KAKEN DB
Kudo, Masataka Browse this author
Sakuragi, Noriaki Browse this author →KAKEN DB
Keywords: review
reactivation of p53
iASPP
microRNA
invasion
Issue Date: 13-Jul-2015
Publisher: Impact Journals
Journal Title: Oncotarget
Volume: 6
Issue: 24
Start Page: 19968
End Page: 19975
Publisher DOI: 10.18632/oncotarget.4847
Abstract: Although mutational inactivation of p53 is found in 50% of all human tumors, a subset of tumors display defective p53 function, but retain wild-type (WT) p53. Here, direct and indirect mechanisms leading to the loss of WT p53 activities are discussed. We summarize the oncogenic roles of iASPP, an inhibitor of WT p53, in promoting proliferation, invasion, drug or radiation-resistance and metastasis. From the therapeutic view, we highlight promising perspectives of microRNA-124, peptide and small molecules that reduce or block iASPP for the treatment of cancer. High iASPP expression enhances proliferation, aggressive behavior, the resistance to radiation/chemotherapy and correlates with poor prognosis in a range of human tumors. Overexpression of iASPP accelerates tumorigenesis and invasion through p53-dependent and p53-independent mechanisms. MicroRNA-124 directly targets iASPP and represses the growth and invasiveness of cancer cells. The disruption of iASPP-p53 interaction by a p53-derived peptide A34 restores p53 function in cancer cells. The inhibition of iASPP phosphorylation with small molecules induces p53-dependent apoptosis and growth suppression. The mechanisms underlying aberrant expression of iASPP in human tumors should be further investigated. Reactivating WT p53 functions by targeting its novel inhibitor iASPP holds promise for potential therapeutic interventions in the treatment of WT p53-containing tumors.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/60531
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 董 培新

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