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pH gradient reversal fuels cancer progression.

Tianyu Zheng1, Marja Jäättelä2, Bin Liu3

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|June 29, 2020
PubMed
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Cancer cells create a reversed pH gradient, with alkaline interiors and acidic exteriors, to fuel their growth. This pH imbalance, driven by altered metabolism and proton removal, presents a therapeutic target for cancer progression.

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Area of Science:

  • Biochemistry
  • Oncology
  • Cell Biology

Background:

  • Malignant tumors exhibit a reversed pH gradient: alkaline intracellularly and acidic extracellularly.
  • Cancer cells shift glucose metabolism to lactate fermentation, producing excess protons.
  • Acid removal pathways and impaired tumor vasculature exacerbate extracellular acidification.

Purpose of the Study:

  • To explain the mechanisms of reversed pH gradient establishment and maintenance in cancer cells.
  • To elucidate how this pH gradient drives cancer progression.
  • To explore therapeutic strategies targeting the reversed pH gradient.

Main Methods:

  • Review of existing literature on cancer cell metabolism and pH regulation.
  • Analysis of proton dynamics in tumor microenvironments.
  • Discussion of potential therapeutic interventions.

Main Results:

  • Cancer cells actively establish and maintain an alkaline cytosol and acidic extracellular environment.
  • The reversed pH gradient significantly contributes to cancer cell proliferation, invasion, and metastasis.
  • Targeting proton extrusion mechanisms and pH regulatory pathways shows promise in preclinical studies.

Conclusions:

  • The reversed pH gradient is a critical hallmark of cancer, essential for tumor growth and progression.
  • Understanding these pH dynamics offers novel therapeutic opportunities for cancer treatment.
  • Targeting cancer-specific pH regulation could lead to more effective anti-cancer therapies.