Fenton reactions drive nucleotide and ATP syntheses in cancer

Journal of Molecular Cell Biology
Huiyan SunYing Xu

Abstract

We present a computational study of tissue transcriptomic data of 14 cancer types to address: what may drive cancer cell division? Our analyses point to that persistent disruption of the intracellular pH by Fenton reactions may be at the root of cancer development. Specifically, we have statistically demonstrated that Fenton reactions take place in cancer cytosol and mitochondria across all the 14 cancer types, based on cancer tissue gene-expression data integrated via the Michaelis-Menten equation. In addition, we have shown that (i) Fenton reactions in cytosol of the disease cells will continuously increase their pH, to which the cells respond by generating net protons to keep the pH stable through a combination of synthesizing glycolytic ATPs and consuming them by nucleotide syntheses, which may drive cell division to rid of the continuously synthesized nucleotides; and (ii) Fenton reactions in mitochondria give rise to novel ways for ATP synthesis with electrons ultimately coming from H2O2, largely originated from immune cells. A model is developed to link these to cancer development, where some mutations may be selected to facilitate cell division at rates dictated by Fenton reactions.

References

Jul 1, 1990·Environmental Health Perspectives·R G Stevens, D R Kalkwarf
Jan 1, 1966·Proceedings of the National Academy of Sciences of the United States of America·A T Jagendorf, E Uribe
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·B BalasubramanianT D Tullius
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Dec 17, 2002·The Journal of Biological Chemistry·Derick HanEnrique Cadenas
Apr 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ka BianFerid Murad
Jun 15, 2005·Annual Review of Biochemistry·Deborah C JohnsonMichael K Johnson
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·D C Wallace
Jan 27, 2007·Blood·Karin FischerMarina Kreutz
Oct 15, 2008·The Journal of Pathology·F PonténM Uhlen
Nov 21, 2008·Cancer Science·Shinya Toyokuni
Dec 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Magnus JohanssonMåns Ehrenberg
Jan 25, 2011·Nature Reviews. Cancer·Rob A CairnsTak W Mak
Jan 31, 2012·Biochimica Et Biophysica Acta·Caiyong Chen, Barry H Paw
Feb 10, 2012·Antioxidants & Redox Signaling·Xiaoke ShiJingxuan Pan
Apr 19, 2013·Nature Reviews. Cancer·Suzy V Torti, Frank M Torti
Oct 26, 2013·Antioxidants & Redox Signaling·Jennifer L MeitzlerJames H Doroshow
Jan 2, 2014·Frontiers in Physiology·Mehdi DamaghiRobert J Gillies
Feb 5, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Pawel SwietachAlzbeta Hulikova
May 14, 2014·Scientific Reports·Jiansheng XieXun Hu
Jul 25, 2014·Cancer & Metabolism·Edoardo Gaude, Christian Frezza
Aug 15, 2014·Proceedings of the National Academy of Sciences of the United States of America·Prakash RadhakrishnanHans H Wandall
Dec 3, 2014·Biochimica Et Biophysica Acta·Enrico Pierluigi SpugniniStefano Fais
Jan 31, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brianne R O'LearyJames J Mezhir
Oct 19, 2017·Nature·Sheng HuiJoshua D Rabinowitz

❮ Previous
Next ❯

Citations

Sep 12, 2019·Journal of Molecular Cell Biology·Luonan Chen
Jul 2, 2020·Scientific Reports·Xiangchun YuYing Xu
Apr 25, 2020·Frontiers in Oncology·Rikki A M BrownPeter J Leedman
Mar 13, 2020·Frontiers in Oncology·Haoyang LiYing Xu
Apr 17, 2020·Frontiers in Oncology·Huiyan SunYing Xu
Jul 1, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Hsing-Yin Chen, Yu-Fen Lin
Mar 19, 2021·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Cheol Keun ParkNam Hoon Cho
Nov 16, 2021·Oncology Reports·Ronald Neil KostoffDemetrios A Spandidos

❮ Previous
Next ❯

Datasets Mentioned

BETA
UA133

Methods Mentioned

BETA
RNA-Seq

Related Concepts

Related Feeds

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.