Редактирование: GNAQ

Guanine nucleotide-binding protein G(q) subunit alpha (Guanine nucleotide-binding protein alpha-q) [GAQ]

==Publications==

{{medline-entry
|title=Active notch protects MAPK activated melanoma cell lines from MEK inhibitor cobimetinib.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33202284
|abstract=The crosstalk between Notch and MAPK pathway plays a role in MEK inhibitor resistance in [[BRAF]]  metastatic melanoma (MM) and promotes migration in [[GNAQ]]  uveal melanoma (UM) cells. We determined the cytotoxicity of combinatorial inhibition of MEK and Notch by cobimetinib and γ-secretase inhibitor (GSI) nirogacestat, in [[BRAF]]  and [[BRAF]] wt MM and [[GNAQ]]  UM cells displaying different Erk1/2 and Notch activation status, with the aim to elucidate the impact of Notch signaling in the response to MEK inhibitor. Overall the combination was synergic in [[BRAF]]  MM and [[GNAQ]]  UM cells and antagonistic in [[BRAF]] wt one. Focusing on UM cells, we found that cobimetinib resulted in G0/G1 phase arrest and apoptosis induction, whereas the combination with GSI increased treatment efficacy by inducing a senescent-like state of cells and by blocking migration towards liver cancer cells. Mechanistically, this was reflected in a strong reduction of cyclin D1, in the inactivation of retinoblastoma protein and in the increase of p27  expression levels. Of note, each drug alone prevented Notch signaling activation resulting in inhibition of c-jun(Ser63) and Hes-1 expression. The combination achieved the strongest inhibition on Notch signaling and on both c-jun(Ser63) and Erk1/2 activation level. In conclusion we unveiled a coordinate action of MAPK and Notch signaling in promoting proliferation of [[BRAF]]  MM and [[GNAQ]]  UM cells. Remarkably, the simultaneous inhibition of MEK and Notch signaling highlighted a role for the second pathway in protecting cells against senescence in [[GNAQ]]  UM cells treated with the MEK inhibitor.

|keywords=* Cobimetinib (PubChem CID: 16222096)
* MEK
* Nirogacestat (PubChem CID:46224413)
* Notch
* Senescence
* Uveal melanoma
|full-text-url=https://sci-hub.do/10.1016/j.biopha.2020.111006
}}
{{medline-entry
|title=[[GNAQ]]  expression initiated in multipotent neural crest cells drives aggressive melanoma of the central nervous system.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31680437
|abstract=Primary leptomeningeal melanocytic neoplasms represent a spectrum of rare tumors originating from melanocytes of the leptomeninges, which are the inner two membranes that protect the central nervous system. Like other non-epithelial melanocytic lesions, they bear frequent oncogenic mutations in the heterotrimeric G protein alpha subunits, [[GNAQ]] or [[GNA11]]. In this study, we used Plp1-creERT to force the expression of oncogenic [[GNAQ]]  in the multipotent neural crest cells of the ventro-medial developmental pathway, beginning prior to melanocyte cell differentiation. We found that this produces leptomeningeal melanocytic neoplasms, including cranial melanocytomas, spinal melanocytomas, and spinal melanomas, in addition to blue nevus-like lesions in the dermis. [[GNAQ]]  drove different phenotypes depending upon when during embryogenesis (E9.5, E10.5, or E11.5) it was induced by tamoxifen and which Cre driver (Plp1-creERT, Tyr-creERT  , or Mitf-cre) was used. Given these differences, we propose that melanocytes go through temporary phases where they become sensitive to the oncogenic effects of [[GNAQ]]  . R26-fs-[[GNAQ]]  ; Plp1-creERT mice will be useful for defining biomarkers for potentially aggressive leptomeningeal melanocytomas and for developing new therapeutics for advanced disease.
|mesh-terms=* Aging
* Animals
* Central Nervous System Neoplasms
* Disease Models, Animal
* Disease Progression
* Embryonic Development
* Female
* GTP-Binding Protein alpha Subunits, Gq-G11
* Male
* Melanocytes
* Melanoma
* Meningeal Neoplasms
* Mice, Transgenic
* Multipotent Stem Cells
* Mutation
* Neoplasm Invasiveness
* Neural Crest
* Nevus
* Skin Neoplasms
* Uveal Neoplasms
|keywords=* GNAQ
* Plp1
* blue nevus
* leptomeningeal melanocytoma
* uveal melanoma
|full-text-url=https://sci-hub.do/10.1111/pcmr.12843
}}