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Literature summary for 3.6.5.2 extracted from

  • Yoo, J.; Brady, S.; Acosta-Alvarez, L.; Rogers, A.; Peng, J.; Sorensen, L.; Wolff, R.; Mleynek, T.; Shin, D.; Rich, C.; Kircher, D.; Bild, A.; Odelberg, S.; Li, D.; Holmen, S.; Grossmann, A.
    The small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state (2019), Cancer Res., 79, 2892-2908 .
    View publication on PubMed

Protein Variants

Protein Variants Comment Organism
Q67L ARF6Q67L promotes spontaneous metastasis from significantly smaller primary tumors than PTENNULL, implying an enhanced ability of ARF6-GTP to drive distant spread. In mice with metastases, there is a dramatic increase in metastatic volume in the ARF6Q67L cohort Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
invadopodium
-
Mus musculus 71437
-
invadopodium
-
Homo sapiens 71437
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Mus musculus
-
GDP + phosphate
-
?
GTP + H2O Homo sapiens
-
GDP + phosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P62330
-
-
Mus musculus P62331
-
-

Source Tissue

Source Tissue Comment Organism Textmining
A-2058 cell
-
Homo sapiens
-
A-375 cell
-
Homo sapiens
-
melanoma cell
-
Homo sapiens
-
melanoma cell primary cells Mus musculus
-
MeWo cell
-
Homo sapiens
-
SK-MEL-2 cell
-
Homo sapiens
-
WM-266-4 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
Mus musculus GDP + phosphate
-
?
GTP + H2O
-
Homo sapiens GDP + phosphate
-
?

Synonyms

Synonyms Comment Organism
ADP-ribosylation factor 6 UniProt Mus musculus
ADP-ribosylation factor 6 UniProt Homo sapiens
Arf6
-
Mus musculus
Arf6
-
Homo sapiens
small GTPase
-
Mus musculus
small GTPase
-
Homo sapiens

General Information

General Information Comment Organism
malfunction ARF6Q67L promotes spontaneous metastasis from significantly smaller primary tumors than PTENNULL, implying an enhanced ability of ARF6-GTP to drive distant spread. ARF6Q67L tumors show upregulation of Pik3r1 expression, which encodes the p85 regulatory subunit of PI3K. Tumor cells expressing ARF6Q67L displays increased PI3K protein levels and activity, enhances PI3K distribution to cellular protrusions, and increases AKT activation in invadopodia. Aberrant ARF6 activation in human melanoma samples is associated with reduced survival Mus musculus
additional information murine ectopic ARF6Q67L mutant increases Matrigel invasion of human A-2058 melanoma cells in vitro. The pan-AKT inhibitor MK2206 and the pan-Class I PI3K inhibitor GSK-0941 both abrogate ARF6Q67L-dependent Matrigel invasion, demonstrating that PI3K signaling is necessary for ARF6-mediated invasion Homo sapiens
physiological function the small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state. ARF6 activation accelerate metastasis and increases lung colonization from circulating melanoma cells, suggesting that the prometastatic function of ARF6 extends to late steps in metastasis. ARF6 is necessary and sufficient for activation of both PI3K and AKT, and PI3K and AKT are necessary for ARF6-mediated invasion. Critical role for ARF6 in multiple steps of the metastatic cascade. ARF6 activation increases metastatic disease burden, a role for ARF6 in proliferation or survival is also possible Homo sapiens
physiological function the small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state. Constitutive activation of the small GTPase ARF6 (ARF6Q67L) is sufficient to accelerate metastasis in mice with BRAFV600E/Cdkn2aNULL melanoma at a similar incidence and severity to Pten loss, a major driver of PI3K activation and melanoma metastasis. ARF6 activation increases lung colonization from circulating melanoma cells, suggesting that the prometastatic function of ARF6 extends to late steps in metastasis. ARF6 is necessary and sufficient for activation of both PI3K and AKT, and PI3K and AKT are necessary for ARF6-mediated invasion. Critical role for ARF6 in multiple steps of the metastatic cascade Mus musculus