Activating mutations in Gαq proteins, which form the α subunit of certain heterotrimeric G proteins, drive uveal melanoma oncogenesis by triggering multiple downstream signaling pathways, including PLC/PKC, Rho/Rac, and YAP. Here we show that the small GTPase ARF6 acts as a proximal node of oncogenic Gαq signaling to induce all of these downstream pathways as well as β-catenin signaling. ARF6 activates these diverse pathways through a common mechanism: the trafficking of GNAQ and β-catenin from the plasma membrane to cytoplasmic vesicles and the nucleus, respectively. Blocking ARF6 with a small-molecule inhibitor reduces uveal melanoma cell proliferation and tumorigenesis in a mouse model, confirming the functional relevance of this pathway and suggesting a therapeutic strategy for Gα-mediated diseases.
Pharmacology, Toxicology and Pharmaceutical Science
4
4%
Chemistry
4
4%
Other
5
4%
Unknown
36
32%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 87. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 December 2024.
All research outputs
#585,227
of 31,439,095 outputs
Outputs from Cancer Cell
#394
of 3,589 outputs
Outputs of similar age
#8,332
of 331,371 outputs
Outputs of similar age from Cancer Cell
#9
of 54 outputs
Altmetric has tracked 31,439,095 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,589 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.0. This one has done well, scoring higher than 88% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 331,371 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 54 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.
