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2016 ; 96
(3
): 1071-91
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The Function of V-ATPases in Cancer
#MMPMID27335445
Stransky L
; Cotter K
; Forgac M
Physiol Rev
2016[Jul]; 96
(3
): 1071-91
PMID27335445
show ga
The vacuolar ATPases (V-ATPases) are a family of proton pumps that couple ATP
hydrolysis to proton transport into intracellular compartments and across the
plasma membrane. They function in a wide array of normal cellular processes,
including membrane traffic, protein processing and degradation, and the coupled
transport of small molecules, as well as such physiological processes as urinary
acidification and bone resorption. The V-ATPases have also been implicated in a
number of disease processes, including viral infection, renal disease, and bone
resorption defects. This review is focused on the growing evidence for the
important role of V-ATPases in cancer. This includes functions in cellular
signaling (particularly Wnt, Notch, and mTOR signaling), cancer cell survival in
the highly acidic environment of tumors, aiding the development of drug
resistance, as well as crucial roles in tumor cell invasion, migration, and
metastasis. Of greatest excitement is evidence that at least some tumors express
isoforms of V-ATPase subunits whose disruption is not lethal, leading to the
possibility of developing anti-cancer therapeutics that selectively target
V-ATPases that function in cancer cells.
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