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Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas.

Publication ,  Journal Article
Shenolikar, S
Published in: J Clin Invest
March 2014

BRAF mutations in aggressive melanomas result in kinase activation. BRAF inhibitors reduce BRAF(V600E) tumors, but rapid resistance follows. In this issue of the JCI, Ma and colleagues report that vemurafenib activates ER stress and autophagy in BRAF(V600E) melanoma cells, through sequestration of the ER chaperone GRP78 by the mutant BRAF and subsequent PERK activation. In preclinical studies, treating vemurafenib-resistant melanoma with a combination of vemurafenib and an autophagy inhibitor reduced tumor load. Further work is needed to establish clinical relevance of this resistance mechanism and demonstrate efficacy of autophagy and kinase inhibitor combinations in melanoma treatment.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

March 2014

Volume

124

Issue

3

Start / End Page

973 / 976

Location

United States

Related Subject Headings

  • Vemurafenib
  • Sulfonamides
  • Proto-Oncogene Proteins B-raf
  • Melanoma
  • Indoles
  • Immunology
  • Humans
  • Endoplasmic Reticulum Stress
  • Endoplasmic Reticulum Chaperone BiP
  • Autophagy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shenolikar, S. (2014). Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas. J Clin Invest, 124(3), 973–976. https://doi.org/10.1172/JCI74609
Shenolikar, Shirish. “Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas.J Clin Invest 124, no. 3 (March 2014): 973–76. https://doi.org/10.1172/JCI74609.
Shenolikar, Shirish. “Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas.J Clin Invest, vol. 124, no. 3, Mar. 2014, pp. 973–76. Pubmed, doi:10.1172/JCI74609.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

March 2014

Volume

124

Issue

3

Start / End Page

973 / 976

Location

United States

Related Subject Headings

  • Vemurafenib
  • Sulfonamides
  • Proto-Oncogene Proteins B-raf
  • Melanoma
  • Indoles
  • Immunology
  • Humans
  • Endoplasmic Reticulum Stress
  • Endoplasmic Reticulum Chaperone BiP
  • Autophagy