Endothelin signaling promotes melanoma tumorigenesis driven by constitutively active GNAQ.

Endothelin signaling promotes melanoma tumorigenesis driven by constitutively active GNAQ.

Publication date: May 26, 2020

The G protein coupled receptor, Endothelin receptor B (EDNRB), is an important regulator of melanocyte survival and proliferation. It acts by stimulating downstream heterotrimeric G proteins, such as G? and G? . Constitutively active, oncogenic versions of G? and G? drive melanomagenesis, but the role of Ednrb in the context of these mutant G proteins has not been previously examined. In this paper, we used a knock-in mouse allele at the Rosa26 locus to force oncogenic GNAQ expression in melanocytes in combination with Ednrb gene knockout. The resulting pathological analysis revealed that every aspect of melanomagenesis driven by GNAQ was inhibited. We conclude that even in the presence of oncogenic G? , the Ednrb receptor activates normal G? and G? proteins. This likely promotes tumorigenesis by activating phospholipase C-beta, the immediate effector of G? . These findings suggest that it might be possible to target upstream receptors to offset the effects of hyperactive G proteins, recognized as the cause of a growing number of human disorders.

Concepts Keywords
Allele Melanoma
Endothelin Branches of biology
Force Cell biology
G Proteins G protein-coupled receptors
Knockout Endothelin B receptor
Locus Peripheral membrane proteins
Melanocyte GNAQ
Melanocytes Uveal melanoma
Melanoma Endothelin receptor
Mutant Melanocyte
Oncogenic Endothelin 3
Phospholipase C
Pigment
Receptor
Receptors
Tumorigenesis

Semantics

Type Source Name
disease MESH melanoma
pathway KEGG Melanoma
disease MESH tumorigenesis
disease MESH uveal melanoma

Original Article

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