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Masannat J
; Purayil HT
; Zhang Y
; Russin M
; Mahmud I
; Kim W
; Liao D
; Daaka Y
Sci Rep
2018[Mar]; 8
(1
): 4879
PMID29559707
show ga
Renal Cell Carcinoma (RCC) is one of the most lethal urological cancers
worldwide. The disease does not present early clinical symptoms and is commonly
diagnosed at an advanced stage. Limited molecular drivers have been identified
for RCC, resulting in the lack of effective treatment for patients with
progressive disease. Ubiquitous ?Arrestin2 (?Arr2) is well established for its
function in the desensitization and trafficking of G protein-coupled receptors.
More recently, ?Arr2 has been implicated in the regulation of fundamental
cellular functions, including proliferation and invasion. We used bioinformatic
and genetic approaches to determine role of ?Arr2 in RCC tumor growth. Analysis
of published human datasets shows that ARRB2 (gene encoding ?Arr2) expression is
increased in RCC tumor compared to normal tissue and that high levels of ARRB2
correlate with worse patient survival. Experimentally, we show that knockout of
ARRB2 decreases rate of RCC cell proliferation and migration in vitro and
xenograft tumor growth in animals. Mechanistically, ?Arr2 regulates c-Src
activity, Cyclin A expression and cell cycle progression that are involved in
tumor growth. These results show that ?Arr2 is a critical regulator of RCC tumor
growth and suggest its utility as a potential marker and drug target to treat
advanced disease.
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