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Journal of Cancer Research and Clinical Oncology

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07.12.2016 | Original Article – Cancer Research

BRAF V600E-dependent role of autophagy in uveal melanoma

verfasst von: Yinu Zhao, Weibin Wang, Irene Min, Brian Wyrwas, Maureen Moore, Rasa Zarnegar, Thomas J. Fahey III

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2017

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Abstract

Background

Autophagy can function in a dual role in cancer development and progression: It can be cytoprotective or contribute to cell death. Therefore, determining the contextual role of autophagy between these two opposing effects is important. So far, little is known about the role of autophagy in uveal melanoma. In the present study, we looked to investigate the autophagic process, as well as its effect on cell survival in uveal melanoma cell lines under stressed conditions (starvation). The possible role of autophagy during BRAF inhibition in uveal melanoma was also sought.

Methods

Two human uveal melanoma cell lines, OCM1A, which harbors the BRAF mutation V600E and Mel 290, which is BRAF wild type, were studied. Autophagy levels were determined by Western blot assay with/without the addition of autophagic flux inhibitor (bafilomycin A1). Cell proliferation was assessed by an MTT assay.

Results

Starvation triggered autophagy in BRAF V600E-mutant OCM1A cells but not in BRAF wild-type Mel 290 cells. Enhanced autophagy helped the OCM1A cells survive under stressed conditions. The BRAF inhibitor vemurafenib upregulated autophagy through suppression of the PI3K/Akt/mTOR/p70S6 K pathway in BRAF V600E-mutant uveal melanoma cells. Autophagy inhibition impaired the treatment efficacy of vemurafenib in BRAF V600E-mutant uveal melanoma cells.

Conclusions

Our data demonstrate that starvation-trigged autophagy, which is BRAF V600E dependent, promotes cancer cell survival in uveal melanoma. Vemurafenib induces autophagic cell death rather than adaptive cell survival in BRAF V600E-mutant melanoma.

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Titel: BRAF V600E-dependent role of autophagy in uveal melanoma
verfasst von: Yinu Zhao
Weibin Wang
Irene Min
Brian Wyrwas
Maureen Moore
Rasa Zarnegar
Thomas J. Fahey III
Publikationsdatum: 07.12.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2017
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2317-y

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BRAF V600E-dependent role of autophagy in uveal melanoma

Abstract

Background

Methods

Results

Conclusions

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Abstract

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Methods

Results

Conclusions

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