Extracellular Acidification Induces Lysosomal Dysregulation.
Acidosis
/ drug therapy
Animals
Antineoplastic Agents
/ therapeutic use
Breast Neoplasms
/ drug therapy
Carcinoma, Ductal, Breast
/ drug therapy
Energy Metabolism
Female
Humans
Hydrogen-Ion Concentration
Lysosomes
/ drug effects
Molecular Targeted Therapy
Tumor Microenvironment
Warburg Effect, Oncologic
Warburg effect
breast cancer
cancer acidosis
cancer metastasis
intracellular pH
lysosomal localization
lysosome dysregulation
targeted therapy
tumor microenvironment
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
13 05 2021
13 05 2021
Historique:
received:
30
03
2021
revised:
05
05
2021
accepted:
09
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
26
10
2021
Statut:
epublish
Résumé
Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the emergence of increasingly aggressive clonal populations. In solid tumors, such as breast ductal carcinoma, the extracellular environment for cells within the nascent tumor is harsh and imposes different types of stress on cells, such as hypoxia, nutrient deprivation, and cytokine inflammation. Acidosis is a constant stressor of most cancer cells due to its production through fermentation of glucose to lactic acid in hypoxic or normoxic regions (Warburg effect). Over a short period of time, acid stress can have a profound effect on the function of lysosomes within the cells exposed to this environment, and after long term exposure, lysosomal function of the cancer cells can become completely dysregulated. Whether this dysregulation is due to an epigenetic change or evolutionary selection has yet to be determined, but understanding the mechanisms behind this dysregulation could identify therapeutic opportunities.
Identifiants
pubmed: 34067971
pii: cells10051188
doi: 10.3390/cells10051188
pmc: PMC8152284
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
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