The FOXO3/PGC-1β signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma.

The Journal of Biological Chemistry
M KumazoeH Tachibana

Abstract

In 95% of patients with pancreatic ductal adenocarcinoma, recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anticancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knock-in/knockdown experiments, and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ co-activator-1β (PGC-1β)/pyruvate dehydrogenase-A1 pathway is essential for CD44 expression and CSC properties. We observed that patients exhibiting high pyruvate dehydrogenase-A1 expression have a poor prognosis. Systemic PGC-1β knock-out mice are fertile and viable and do not exhibit an overt phenotype under normal conditions. This suggests that cGMP induction and PGC-1β inhibition represent potential strategies for treating patients with pancreatic ductal adenocarcinoma.

References

Jan 1, 1983·Reviews of Physiology, Biochemistry and Pharmacology·O H Wieland
Jun 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H A BurrisD D Von Hoff
Jul 12, 2003·Science·Diego H CastrillonRonald A DePinho
Aug 10, 1956·Science·O WARBURG
Oct 19, 2006·Trends in Genetics : TIG·Renée van Amerongen, Anton Berns
Feb 7, 2007·Cancer Research·Chenwei LiDiane M Simeone
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Junichiro SonodaRonald M Evans
Aug 19, 2009·Nature Reviews. Clinical Oncology·Gregory SergeantBaki Topal
Nov 13, 2009·Development·Christina Lindsey Hammond, Stefan Schulte-Merker
Jun 12, 2010·Cardiology in Review·Vaughn E NossamanPhilip J Kadowitz
Dec 15, 2010·Nature Reviews. Clinical Oncology·Naoko TakebeS Percy Ivy
Feb 3, 2011·The Journal of Clinical Investigation·Barbara Varnum-FinneyIrwin D Bernstein
May 13, 2011·The New England Journal of Medicine·Thierry ConroyUNKNOWN PRODIGE Intergroup
May 31, 2011·Lancet·Audrey VincentMichael Goggins
Jun 28, 2011·The EMBO Journal·Ying-Jhen SuJia-Lin Lee
Jun 8, 2012·The New England Journal of Medicine·Aleksandar SekulicAxel Hauschild
Jan 7, 2015·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Sep 10, 2015·Molecular and Cellular Biology·Kurt W FisherRobert E Lewis
Oct 17, 2015·Annual Review of Medicine·Alessia Buglioni, John C Burnett
Jun 9, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shujie ZhaoJames W Freeman
Nov 29, 2016·Oncogene·M KumazoeH Tachibana

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Citations

Feb 28, 2020·Molecular Nutrition & Food Research·Jaehoon BaeHirofumi Tachibana
Dec 14, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Yaohan WangPeitong Zhang
Feb 8, 2020·Journal of Cancer Research and Clinical Oncology·Eduardo MartinezMegan Keniry
Jan 6, 2021·Cells·Neerajana DattaMrinal K Ghosh
Apr 4, 2021·Antioxidants·Giuseppina BarreraStefania Pizzimenti

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