Dear Scientific Community:
I am looking for an effective alternative readout of glycolysis inhibition in cancer cells.
In addition to monitor the production of Lactate or Glucose uptake (that are the classic experiments), do you know if there are some genes that is down--regulated or up-regulated after glycolysis inhibition ? (for example, some gene of OXPHOS)
thank you for the help
Marco
Hello Marco Cordani
You can refer to the research article given below.
https://www.jbc.org/article/S0021-9258(20)87213-5/pdf
Highlight:
Unique sensitivity of tumor cells to the inhibition of glycolysis is a good target for anticancer therapy. Here, we demonstrate that the pharmacologically activated tumor suppressor p53 mediates the inhibition of glycolytic enzymes in cancer cells in vitro and in vivo. We showed that p53 binds to the promoters of metabolic genes and represses their expression, including glucose transporters SLC2A12 (GLUT12) and SLC2A1 (GLUT1). Furthermore, p53-mediated repression of transcription factors c-Myc and HIF1alpha, key drivers of ATP-generating pathways in tumors, contributed to ATP production block. Inhibition of c-Myc by p53 mediated the ablation of several glycolytic genes in normoxia, whereas in hypoxia downregulation of HIF1alpha contributed to this effect. We identified Sp1 as a transcription cofactor cooperating with p53 in the ablation of metabolic genes. Using different approaches, we demonstrated that glycolysis block contributes to the robust induction of apoptosis by p53 in cancer cells. Taken together, our data suggest that tumor-specific reinstatement of p53 function targets the “Achilles heel” of cancer cells (i.e. their dependence on glycolysis), which could contribute to the tumor-selective killing of cancer cells by pharmacologically activated p53.
I hope this is helpful.
Best,
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