Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
An inverted pH gradient across the cell membranes is a typical feature of malignant cancer cells that are characterized by extracellular acidosis and cytosol alkalization. These dysregulations are able to create a unique milieu that favors tumor progression, metastasis and chemo/immune-resistance traits of solid tumors. A key event mediating tumor cell pH alterations is an aberrant activation of ion channels and proton pumps such as (H+)-vacuolar-
ATPase
(V-ATPase).
TM9SF4
is a poorly characterized transmembrane protein that we have recently shown to be related to cannibal behavior of metastatic melanoma cells. Here, we demonstrate that
TM9SF4
represents a novel V-
ATPase
-associated protein involved in V-
ATPase
activation. We have observed in HCT116 and SW480 colon cancer cell lines that
TM9SF4
interacts with the ATP6V1H subunit of the V-
ATPase
V1 sector. Suppression of
TM9SF4
with small interfering RNAs strongly reduces assembly of V-
ATPase
V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity. Such effects are associated with a significant inhibition of the invasive behavior of colon cancer cells and with an increased sensitivity to the cytotoxic effects of 5-fluorouracil. Our study shows for the first time the important role of
TM9SF4
in the aberrant constitutive activation of the V-
ATPase
, and the development of a malignant phenotype, supporting the potential use of
TM9SF4
as a target for future anticancer therapies.
...
PMID:TM9SF4 is a novel V-ATPase-interacting protein that modulates tumor pH alterations associated with drug resistance and invasiveness of colon cancer cells. 2565 76
