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Increased Heme Synthesis in Ovarian Cancer and Triple Negative Breast Cancer Cells Leads to Downregulation of Glycolysis, Mitochondrial Respiration, and Cell Migration.
Author(s) -
Kaur Pritpal,
Nagar Shreya,
Bhagwat Madhura,
Padmanabhan Sveta,
Gaire Bijaya,
Vancura Ales
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.01940
Subject(s) - glycolysis , citric acid cycle , oxidative phosphorylation , heme , downregulation and upregulation , anaerobic glycolysis , warburg effect , biochemistry , cancer cell , mitochondrion , chemistry , microbiology and biotechnology , biology , cancer , metabolism , enzyme , genetics , gene
Cancer cells undergo a complex rearrangement of metabolic pathways involved in biosynthetic processes to support tumor initiation and progression. Targeting glycolysis and TCA cycle that provide precursors for biosynthetic pathways emerged as a potential therapeutic strategy in some cancers. Heme has a potential to regulate both glycolysis and TCA cycle. Heme serves as a prosthetic group in proteins and enzymes that sense, transport, or use oxygen, such as hemoglobin, myoglobin, cytochrome complexes, catalases, and cyclooxygenases. Heme is also required for ATP production by the mitochondrial electron transport chain (ETC) and oxidative phosphorylation (OXPHOS). The first and rate‐limiting step in heme synthesis is production of 5‐aminolevulinic acid (ALA). In this study, we show that promoting heme synthesis by ALA supplementation in ovarian cancer and triple negative breast cancer cells leads to downregulation of glycolysis and lactate production, mitochondrial respiration, as well as cell migration. The mechanism responsible for reduced glycolysis and cell migration involves destabilization of heme‐regulated transcription factor Bach1. Support or Funding Information Supported by NIH GM120710