How protons pave the way to aggressive cancers
Research output: Contribution to journal › Review › Research › peer-review
Standard
How protons pave the way to aggressive cancers. / Swietach, Pawel; Boedtkjer, Ebbe; Pedersen, Stine Falsig.
In: Nature Reviews Cancer, Vol. 23, 2023, p. 825-841.Research output: Contribution to journal › Review › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - How protons pave the way to aggressive cancers
AU - Swietach, Pawel
AU - Boedtkjer, Ebbe
AU - Pedersen, Stine Falsig
N1 - Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - Cancers undergo sequential changes to proton (H+) concentration and sensing that are consequences of the disease and facilitate its further progression. The impact of protonation state on protein activity can arise from alterations to amino acids or their titration. Indeed, many cancer-initiating mutations influence pH balance, regulation or sensing in a manner that enables growth and invasion outside normal constraints as part of oncogenic transformation. These cancer-supporting effects become more prominent when tumours develop an acidic microenvironment owing to metabolic reprogramming and disordered perfusion. The ensuing intracellular and extracellular pH disturbances affect multiple aspects of tumour biology, ranging from proliferation to immune surveillance, and can even facilitate further mutagenesis. As a selection pressure, extracellular acidosis accelerates disease progression by favouring acid-resistant cancer cells, which are typically associated with aggressive phenotypes. Although acid–base disturbances in tumours often occur alongside hypoxia and lactate accumulation, there is now ample evidence for a distinct role of H+-operated responses in key events underpinning cancer. The breadth of these actions presents therapeutic opportunities to change the trajectory of disease.
AB - Cancers undergo sequential changes to proton (H+) concentration and sensing that are consequences of the disease and facilitate its further progression. The impact of protonation state on protein activity can arise from alterations to amino acids or their titration. Indeed, many cancer-initiating mutations influence pH balance, regulation or sensing in a manner that enables growth and invasion outside normal constraints as part of oncogenic transformation. These cancer-supporting effects become more prominent when tumours develop an acidic microenvironment owing to metabolic reprogramming and disordered perfusion. The ensuing intracellular and extracellular pH disturbances affect multiple aspects of tumour biology, ranging from proliferation to immune surveillance, and can even facilitate further mutagenesis. As a selection pressure, extracellular acidosis accelerates disease progression by favouring acid-resistant cancer cells, which are typically associated with aggressive phenotypes. Although acid–base disturbances in tumours often occur alongside hypoxia and lactate accumulation, there is now ample evidence for a distinct role of H+-operated responses in key events underpinning cancer. The breadth of these actions presents therapeutic opportunities to change the trajectory of disease.
U2 - 10.1038/s41568-023-00628-9
DO - 10.1038/s41568-023-00628-9
M3 - Review
C2 - 37884609
AN - SCOPUS:85174977264
VL - 23
SP - 825
EP - 841
JO - Nature Reviews. Cancer
JF - Nature Reviews. Cancer
SN - 1474-175X
ER -
ID: 372183921