Supplementary Figure S1 from Effects of Oncogenic Gαq and Gα11 Inhibition by FR900359 in Uveal Melanoma

Lapadula, Dominic; Farias, Eduardo; Randolph, Clinita E.; Purwin, Timothy J.; McGrath, Dougan; Charpentier, Thomas H.; Zhang, Lihong; Wu, Shihua; Terai, Mizue; Sato, Takami; Tall, Gregory G.; Zhou, Naiming; Wedegaertner, Philip B.; Aplin, Andrew E.; Aguirre-Ghiso, Julio; Benovic, Jeffrey L.

doi:10.1158/1541-7786.22513482.v1

15417786mcr180574-sup-202813_2_supp_5178800_pck9b3.pdf (257.4 kB)

Supplementary Figure S1 from Effects of Oncogenic Gα_q and Gα₁₁ Inhibition by FR900359 in Uveal Melanoma

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posted on 2023-04-03, 16:48 authored by Dominic Lapadula, Eduardo Farias, Clinita E. Randolph, Timothy J. Purwin, Dougan McGrath, Thomas H. Charpentier, Lihong Zhang, Shihua Wu, Mizue Terai, Takami Sato, Gregory G. Tall, Naiming Zhou, Philip B. Wedegaertner, Andrew E. Aplin, Julio Aguirre-Ghiso, Jeffrey L. Benovic

GNAQ and GNA11 sequence analysis of UM002B cells.

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ARTICLE ABSTRACT

Uveal melanoma is the most common intraocular tumor in adults and often metastasizes to the liver, leaving patients with few options. Recurrent activating mutations in the G proteins, Gαq and Gα11, are observed in approximately 93% of all uveal melanomas. Although therapeutic intervention of downstream Gαq/11 targets has been unsuccessful in treating uveal melanoma, we have found that the Gαq/11 inhibitor, FR900359 (FR), effectively inhibits oncogenic Gαq/11 signaling in uveal melanoma cells expressing either mutant Gαq or Gα11. Inhibition of oncogenic Gαq/11 by FR results in cell-cycle arrest and induction of apoptosis. Furthermore, colony formation is prevented by FR treatment of uveal melanoma cells in 3D-cell culture, providing promise for future in vivo studies. This suggests direct inhibition of activating Gαq/11 mutants may be a potential means of treating uveal melanoma. Oncogenic Gαq/11 inhibition by FR900359 may be a potential treatment option for those with uveal melanoma.

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Keywords

Cell Signaling Guanine nucleotide binding proteins and effectors Pharmacology Molecular pharmacology

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