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Targeting endosomal pH for cancer chemotherapy
Fabrice Lucien1,2, Roxane R Lavoie1,2, Claire M Dubois1,2
1Division of Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Canada.
Molecular & Cellular Oncology
|September 26, 2018
Summary
Altered pH in cancer cells contributes to chemoresistance. Our study reveals that the endosomal pH regulator, sodium/hydrogen exchanger 6 (NHE6), is aberrantly distributed in hypoxic cancer cells, causing this resistance.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Altered pH homeostasis is a hallmark of cancer, contributing to various cancer progression aspects.
- Cancer cells exhibit dysregulated pH, which is implicated in therapeutic resistance, particularly chemoresistance.
Purpose of the Study:
- To elucidate the novel mechanism by which dysregulated pH in hypoxic cancer cells leads to chemoresistance.
- To investigate the role of the endosomal pH regulator, sodium/hydrogen exchanger 6 (NHE6), in this process.
Main Methods:
- Analysis of pH homeostasis in cancer cells.
- Investigation of cellular distribution of sodium/hydrogen exchanger 6 (NHE6) in hypoxic conditions.
- Assessment of the impact of NHE6 dysregulation on chemoresistance.
Main Results:
- Hypoxic cancer cells exhibit dysregulated pH homeostasis.
- Aberrant cellular distribution of sodium/hydrogen exchanger 6 (NHE6) was identified in hypoxic cancer cells.
- This aberrant NHE6 distribution is mechanistically linked to chemoresistance.
Conclusions:
- Dysregulated pH in hypoxic cancer cells, driven by aberrant NHE6 distribution, is a novel mechanism of chemoresistance.
- Targeting NHE6 or pH regulation may offer new therapeutic strategies for overcoming chemoresistance in cancer.
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