RACK1 deficiency synergizes with all-trans retinoic acid to induce apoptosis in human acute promyelocytic leukemia cells

Molecular and Cellular Biochemistry
Huifang WuJing Wang

Abstract

As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in the treatment of acute promyelocytic leukemia (APL). However, the clinical application of ATRA has strict limitations, for its severe side effects due to the accumulation of peripheral blood leukocytes. The scaffold protein RACK1 (Receptor for activated C kinase 1), which regulates multiple signaling pathways, has been proposed to contribute to the survival of leukemic progenitors. But it remains unclear whether it is also involved in the oncogenic growth of APL. In the present study, we demonstrate that silencing of endogenous RACK1 expression synergized with ATRA to promote the death of NB4 and HL-60 APL cells without effect on cell differentiation induced by ATRA. Interestingly, RACK1 knockdown combined with ATRA treatment mainly induces apoptosis. It is distinct to the necrotic cell death induced by idarubicin in combination with ATRA, a regimen extensively used in the clinic to prevent neutrophil accumulation. Further exploration revealed that the lysosome-autophagy pathway is likely to be responsible for the anti-apoptotic role of RACK1. Taken together, our findings indicate that RACK1 is essential in maintaining the malignant featu...Continue Reading

References

Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·D RonD Mochly-Rosen
Feb 24, 2007·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Guang-Biao ZhouZhu Chen
May 8, 2007·Cancer Cell·Pablo Lopez-BergamiZe'ev Ronai
Oct 7, 2008·Nature Cell Biology·Kyoko ArimotoMutsuhiro Takekawa
Feb 28, 2009·The New England Journal of Medicine·Jonathan D Licht
Mar 31, 2010·PloS One·Fabienne De Toni-CostesClaire Racaud-Sultan
Sep 3, 2010·Nature Cell Biology·Noboru Mizushima, Beth Levine
Jan 12, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alan BurnettBob Löwenberg
Aug 21, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yuanyuan GuoJiyan Zhang
Sep 4, 2013·Molecular and Cellular Biochemistry·Dalin ZhangJiyan Zhang
Jun 3, 2014·Oncogene·J-J Li, D Xie
Aug 26, 2014·Biological Chemistry·Pavel DavidovichSeamus J Martin
Apr 9, 2016·The Journal of Community and Supportive Oncology·Nirav N ShahAlexander Perl
Feb 6, 2017·Cellular Signalling·Maja Holch NielsenLasse Bohl Jenner
Mar 25, 2017·Cellular Signalling·Deirdre Duff, Aideen Long
Jul 29, 2017·Nature Reviews. Cancer·Jean M Mulcahy LevyAndrew Thorburn

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Methods Mentioned

BETA
flow cytometry
FACS
ELISA

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