Scaffold KSR2 overexpression is associated with melanoma A375 cells resistance to Vemurafenib
Main Article Content
Abstract
A large number of tumors shows a deregulation of the pathway RAS-RAF-MEK-ERK. Most of cases of melanoma are caused by the mutation V600E of BRAF, that leads to the constitutive activation of this kinase and of the MAPK pathway. One of the most important BRAF V600E inhibitor used against melanoma is vemurafenib.
Extension study of melanoma patients with BRAF V600E tumors shows that vemurafenib treatment of these metastatic melanomas causes complete or partial tumor regression. However, the majority of patients eventually develops resistance or presents intrinsic resistance against this drug, and the tumor becomes more aggressive.
Several mechanisms of resistance to BRAF inhibitors have been described. In most of these mechanisms the resistance to BRAF inhibitors results from reactivation of MEK-ERK pathway. Scaffold KSR2 is an important modulator of ERK-MAPK signalling pathway. In this study, we investigated the role of KSR2 in vemurafenib-treated melanoma cells.
We found that treatment with the BRAF-selective inhibitor vemurafenib induced the expression of KSR2 in A375 human melanoma cells. Interestingly, the KSR2 overexpression increased the melanoma cells growth after treatment with vemurafenib. These results suggest that scaffold KSR2 could play an important role in the mechanism of resistance of melanoma against BRAF inhibitor vemurafenib.
Article Details
How to Cite
BOTTIGLIONE, Federica; GIURISATO, Emanuele.
Scaffold KSR2 overexpression is associated with melanoma A375 cells resistance to Vemurafenib.
Medical Research Archives, [S.l.], v. 2, n. 7, nov. 2015.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/384>. Date accessed: 27 dec. 2024.
Keywords
scaffold KSR2; ERK-MAPK; melanoma; drug resistance
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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Forsea, A. M., Del Marmol, V., de Vries, E., Bailey, E. E., & Geller, A.C. (2012). Melanoma incidence and mortality in Europe: new estimates, persistent disparities. Br. J. Dermatol. 167, 1124–1130. doi: 10.1111/j.1365-2133.2012.11125.x.
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