The creatine-phosphagen system is mechanoresponsive in pancreatic adenocarcinoma and fuels invasion and metastasis.

Nature Metabolism
Vassilis PapalazarouLaura M Machesky

Abstract

Pancreatic ductal adenocarcinoma is particularly metastatic, with dismal survival rates and few treatment options. Stiff fibrotic stroma is a hallmark of pancreatic tumours, but how stromal mechanosensing affects metastasis is still unclear. Here, we show that mechanical changes in the pancreatic cancer cell environment affect not only adhesion and migration, but also ATP/ADP and ATP/AMP ratios. Unbiased metabolomic analysis reveals that the creatine-phosphagen ATP-recycling system is a major mechanosensitive target. This system depends on arginine flux through the urea cycle, which is reflected by the increased incorporation of carbon and nitrogen from L-arginine into creatine and phosphocreatine on stiff matrix. We identify that CKB is a mechanosensitive transcriptional target of YAP, and thus it increases phosphocreatine production. We further demonstrate that the creatine-phosphagen system has a role in invasive migration, chemotaxis and liver metastasis of cancer cells.

References

Jul 1, 1993·Biophysical Journal·C S PeskinG F Oster
Jul 14, 2000·Physiological Reviews·M Wyss, R Kaddurah-Daouk
Feb 22, 2001·Annual Review of Physiology·W R Ellington
Feb 13, 2008·IEEE Transactions on Image Processing : a Publication of the IEEE Signal Processing Society·P ThévenazM Unser
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jennifer P MortonOwen J Sansom
May 11, 2010·Seminars in Cancer Biology·Edna Cukierman, Daniel E Bassi
Jun 4, 2010·Current Protocols in Cell Biology·Justin R Tse, Adam J Engler
Oct 5, 2010·Nature Cell Biology·David M BryantKeith E Mostov
Nov 15, 2011·Nature Cell Biology·Masha Prager-KhoutorskyAlexander D Bershadsky
Jan 3, 2012·Current Opinion in Cell Biology·Jose Javier Bravo-CorderoJohn Condeelis
Mar 25, 2014·Nature Cell Biology·Giovanni SorrentinoGiannino Del Sal
May 28, 2014·Methods in Enzymology·Martin PelletierRichard M Siegel
Nov 22, 2014·Nature Reviews. Molecular Cell Biology·Caroline BonnansZena Werb
Jan 17, 2015·Nature Reviews. Cancer·Toshiro MoroishiKun-Liang Guan
Mar 10, 2015·Nature Cell Biology·Wenqi WangJunjie Chen
Mar 10, 2015·Nature Cell Biology·Jung-Soon MoKun-Liang Guan
Mar 23, 2015·The EMBO Journal·Elena EnzoSirio Dupont
May 20, 2015·Nature Cell Biology·Bruno Costa-SilvaDavid Lyden
Feb 26, 2016·Nature·Peter BaileySean M Grimmond
Jun 9, 2016·Methods in Molecular Biology·Olivia SusantoRobert H Insall
Jul 13, 2016·European Journal of Cell Biology·Eric L Hastie, David R Sherwood
Nov 8, 2016·Nature Cell Biology·Yekaterina A MiroshnikovaValerie M Weaver
Feb 12, 2017·Cell·Matthew G Vander Heiden, Ralph J DeBerardinis
Jun 16, 2017·Molecular Biology of the Cell·Max-Hinderk SchulerBrian Cunniff
Jun 18, 2017·Molecular Cell·Daniel Garcia, Reuben J Shaw
Jul 25, 2017·Trends in Cell Biology·Costas A Lyssiotis, Alec C Kimmelman
Sep 28, 2017·Nature Reviews. Molecular Cell Biology·Tito PancieraStefano Piccolo
Dec 31, 2017·Gastroenterology·Claire VenninPaul Timpson
Jan 10, 2018·The EMBO Journal·Guillermo López-DoménechJosef T Kittler
May 22, 2018·Frontiers in Oncology·Vasiliki Gkretsi, Triantafyllos Stylianopoulos
Oct 6, 2018·International Journal of Molecular Sciences·Cameron WalkerArmando Del Río Hernández

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Citations

Mar 5, 2020·Nature Reviews. Cancer·Ulrike Harjes
Jul 23, 2020·Nature Metabolism·Maria V Liberti, Kivanc Birsoy
Jun 5, 2020·Nature Reviews. Endocrinology·Lawrence Kazak, Paul Cohen
Mar 21, 2020·Signal Transduction and Targeted Therapy·Jawad FaresYoussef Fares
Oct 9, 2020·Development·Vassilis PapalazarouLaura M Machesky
Nov 15, 2020·Nature Reviews. Molecular Cell Biology·Patrizia RomaniSirio Dupont
Feb 8, 2021·Trends in Cell Biology·Aastha Garde, David R Sherwood
Feb 17, 2021·Nature Reviews. Cancer·Thomas R Cox
Sep 26, 2020·Current Opinion in Cell Biology·Vassilis Papalazarou, Laura M Machesky
Apr 17, 2020·Signal Transduction and Targeted Therapy·Jawad FaresYoussef Fares
Apr 30, 2021·Cell Metabolism·Matthew R ZanotelliCynthia A Reinhart-King
Apr 21, 2021·Nature Metabolism·Tom M J EversAlireza Mashaghi
May 12, 2021·Disease Models & Mechanisms·James Drew, Laura M Machesky
May 22, 2021·Cell Metabolism·Kevin M TharpValerie M Weaver
Jun 3, 2021·Cell Metabolism·Damien Lagarde, Lawrence Kazak
Jul 15, 2021·Current Biology : CB·Thomas MacVicar, Thomas Langer
Aug 20, 2021·Cellular and Molecular Life Sciences : CMLS·Andrey S MarchevMilen I Georgiev
Sep 3, 2021·Journal of Cell Science·Aurore Claude-TaupinNicolas Dupont
Sep 22, 2021·Molecular Cell·Vasileios Papalazarou, Oliver D K Maddocks

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Methods Mentioned

BETA
fluorescence-activated cell sorting
dissection
GTPase
FCS
FACS
transfection
atomic force microscopy
Protein Assay
electrophoresis
Profiler

Software Mentioned

CellProfiler
CellProfiler Analyst
Fiji
HALO Image Analysis
ProteoWizard
custom
SIMCA
ImageJ
Zeiss ZEN
Rstudio

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