PKCδ maintains phenotypes of tumor initiating cells through cytokine-mediated autocrine loop with positive feedback

Oncogene
R-K KimS-J Lee

Abstract

The existence of tumor initiating cells (TICs) has been emerged as a good therapeutic target for treatment of glioblastoma that is the most aggressive brain tumor with poor prognosis. However, the molecular mechanisms that regulate the phenotypes of TICs still remain obscure. In this study, we found that PKCδ, among PKC isoforms, is preferentially activated in TICs and acts as a critical regulator for the maintenance of TICs in glioblastoma. By modulating the expression levels or activity of PKCδ, we demonstrated that PKCδ promotes self-renewal and tumorigenic potentials of TICs. Importantly, we found that the activation of PKCδ persists in TICs through an autocrine loop with positive feedback that was driven by PKCδ/STAT3/IL-23/JAK signaling axis. Moreover, for phenotypes of TICs, we showed that PKCδ activates AKT signaling component by phosphorylation specifically on Ser473. Taken together, we proposed that TICs regulate their own population in glioblastoma through an autocrine loop with positive feedback that is driven by PKCδ-dependent secretion of cytokines.

References

Jun 1, 1997·Molecular and Cellular Biology·Z LuD A Foster
Aug 1, 1997·Molecular and Cellular Biology·J SasseF Horn
Sep 12, 1997·Science·J E Darnell
Mar 11, 1999·Journal of Receptor and Signal Transduction Research·M H Heim
Apr 14, 2000·Frontiers in Bioscience : a Journal and Virtual Library·J D Black
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·N UchidaI L Weissman
Sep 21, 2002·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Normand LaperriereUNKNOWN Cancer Care Ontario Practice Guidelines Initiative Neuro-Oncology Disease Site Group
Oct 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Oleg N SuslovDennis A Steindler
Nov 6, 2002·Journal of Biochemistry·Shigeru Nakashima
Feb 1, 2003·Lancet·Anthony BehinJean-Yves Delattre
Feb 3, 2004·Journal of Cellular and Molecular Medicine·Alakananda Basu
Nov 19, 2004·Nature·Sheila K SinghPeter B Dirks
Jun 28, 2005·Journal of Neuropathology and Experimental Neurology·Hiroko Ohgaki, Paul Kleihues
Oct 18, 2005·Cancer Cell·Michael D TaylorRichard J Gilbertson
Nov 24, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Zhenfeng DuanMichael V Seiden
Aug 4, 2007·Biochemical and Biophysical Research Communications·Akihito InagakiToru Iwama
Oct 24, 2007·International Journal of Cancer. Journal International Du Cancer·Jian WangPer Ø Enger
Feb 23, 2008·The Journal of Biological Chemistry·Akio SoedaToru Iwama
Apr 3, 2008·Neurosurgery·Alfred T OgdenJeffrey N Bruce
Jun 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter B Dirks
Jun 19, 2008·Laboratory Investigation; a Journal of Technical Methods and Pathology·Kyeung Min JooDo-Hyun Nam
Jun 27, 2008·Neuron·Charles D Stiles, David H Rowitch
Sep 6, 2008·Science·D Williams ParsonsKenneth W Kinzler
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
May 12, 2009·Cell Stem Cell·Myung Jin SonHoward A Fine
Aug 18, 2009·Molecular and Cellular Neurosciences·Yongjoon SuhFrancesca Ciccolini
Dec 8, 2009·Cancer Cell·Bijay S JaiswalSomasekar Seshagiri
Aug 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gregor AufMichel Moenner
Nov 26, 2010·TheScientificWorldJournal·Alakananda Basu, Deepanwita Pal
Jan 12, 2013·Stem Cells·Paola BresciaGiuliana Pelicci

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