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

Oncotarget
Peixin DongNoriaki Sakuragi

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 sh...Continue Reading

References

May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·U M MollG Riou
May 15, 1997·Nature·Y HauptM Oren
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·M M SugrueS A Aaronson
Feb 29, 2000·The Journal of Biological Chemistry·Z ZouS Srivastava
Oct 24, 2001·Cell·H VaziriR A Weinberg
Aug 3, 2002·Nature Reviews. Cancer·Gerry MelinoKaren H Vousden
Sep 18, 2002·The Journal of Experimental Medicine·Alex I ZaikaUte M Moll
Jan 14, 2003·Nature Genetics·Daniele BergamaschiXin Lu
Dec 21, 2004·Leukemia Research·Xinwei ZhangJianxiang Wang
Dec 21, 2004·Cancer Cell·Sandrine Valsesia-WittmannAlain Puisieux
Aug 18, 2006·Nature Reviews. Cancer·Charles J Sherr
Jan 11, 2007·British Journal of Cancer·A Sullivan, X Lu
Jun 16, 2007·Experimental Cell Research·Magdalena J LaskaBjørn A Nexø
May 13, 2008·The Journal of Biological Chemistry·Sreerama ShettyRashmi S Shetty
Jul 3, 2008·Cancer Research·Helen S Bell, Kevin M Ryan
Sep 18, 2008·Cancer Investigation·Ze-Jun LiuJie Chen
Oct 7, 2008·Annual Review of Pharmacology and Toxicology·Sanjeev Shangary, Shaomeng Wang
Oct 29, 2008·Oncogene·E C PietschM E Murphy
Dec 17, 2008·Cancer Research·Christian J BraunMatthias Dobbelstein
Dec 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bo SongJingfang Ju
Feb 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mohit SachdevaYin-Yuan Mo
May 19, 2009·Nature Cell Biology·Shu-Ping WangPan-Chyr Yang
Jul 18, 2009·Nature Reviews. Cancer·G Paolo Dotto
Jul 25, 2009·Nature·Hiroshi I SuzukiKohei Miyazono
Sep 10, 2009·Cell·Mark ShackletonSean J Morrison
Sep 16, 2009·Carcinogenesis·Shikhar SharmaPeter A Jones
Feb 19, 2010·Translational Oncology·Zhen Wang, Yi Sun
Jul 14, 2010·Epigenetics : Official Journal of the DNA Methylation Society·Xian Wang, Hongchuan Jin
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg

❮ Previous
Next ❯

Citations

Jul 24, 2018·Frontiers in Oncology·Peixin DongHidemichi Watari
Apr 13, 2017·Journal of Experimental & Clinical Cancer Research : CR·Ying XiongZe-Biao Ma
Feb 19, 2019·Chemical Science·Anat Iosub-AmirRachel Nechushtai

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis