RT Journal Article
T1 Gomesin inhibits melanoma growth by manipulating key signaling cascades that control cell death and proliferation
A1 Ikonomopoulou, Maria P.
A1 Fernández Rojo, Manuel A.
A1 Pineda, Sandy S.
A1 Cabezas Sáinz, Pablo
A1 Winnen, Brit
A1 Morales, Rodrigo A.V.
A1 Brust, Andreas
A1 Sánchez Piñón, Laura
A1 Alewood, Paul F.
A1 Ramm, Grant A.
A1 Miles, John J.
A1 King, Glenn F.
K1 Biologics
K1 Drug discovery
AB Consistent with their diverse pharmacology, peptides derived from venomous animals have been developed as drugs to treat disorders as diverse as hypertension, diabetes and chronic pain. Melanoma has a poor prognosis due in part to its metastatic capacity, warranting further development of novel targeted therapies. This prompted us to examine the anti-melanoma activity of the spider peptides gomesin (AgGom) and a gomesin-like homolog (HiGom). AgGom and HiGom dose-dependently reduced the viability and proliferation of melanoma cells whereas it had no deleterious effects on non-transformed neonatal foreskin fibroblasts. Concordantly, gomesin-treated melanoma cells showed a reduced G0/G1 cell population. AgGom and HiGom compromised proliferation of melanoma cells via activation of the p53/p21 cell cycle check-point axis and the Hippo signaling cascade, together with attenuation of the MAP kinase pathway. We show that both gomesin peptides exhibit antitumoral activity in melanoma AVATAR-zebrafish xenograft tumors and that HiGom also reduces tumour progression in a melanoma xenograft mouse model. Taken together, our data highlight the potential of gomesin for development as a novel melanoma-targeted therapy
PB Nature Publishing Group
YR 2018
FD 2018
LK http://hdl.handle.net/10347/22717
UL http://hdl.handle.net/10347/22717
LA eng
NO Ikonomopoulou, M.P., Fernandez-Rojo, M.A., Pineda, S.S. et al. Gomesin inhibits melanoma growth by manipulating key signaling cascades that control cell death and proliferation. Sci Rep 8, 11519 (2018). https://doi.org/10.1038/s41598-018-29826-4
NO This work was supported by Perpetual IMPACT Grant IDIPAP2015/1585 (to J.J.M.), Discovery Grants DP1095728 (to J.J.M.) and DP130103813 (to G.F.K.) from the Australian Research Council, and by QIMR Berghofer Medical Research Institute crowd funding and salary support (to M.P.I.). M.P.I. is a “Marie Curie” AMAROUT Fellow. M.A.F.R. is a fellow supported by the Talent Program from the Madrid Government of Spain (Grant No. T1-BIO-1854 to M.A.F.R.). J.J.M. is supported by a NHMRC Career Development Fellowship (APP1131732) and G.F.K. by a NHMRC Principal Research Fellowship (APP1136889)
DS Minerva
RD 30 abr 2026