Idioma:

Systematic mapping of BCL-2 gene dependencies in cancer reveals molecular determinants of BH3 mimetic sensitivity

Soderquist, Ryan S ; Crawford, Lorin ; Liu, Esther ; Lu, Min ; Agarwal, Anika ; Anderson, Gray R ; Lin, Kevin H ; Winter, Peter S ; Cakir, Merve ; Wood, Kris C

Nature communications, 2018-08, Vol.9 (1), p.3513-13, Article 3513 [Periódico revisado por pares]

England: Nature Publishing Group

Texto completo disponível

Citações Citado por

Enviar para

Título:
Systematic mapping of BCL-2 gene dependencies in cancer reveals molecular determinants of BH3 mimetic sensitivity
Autor: Soderquist, Ryan S ; Crawford, Lorin ; Liu, Esther ; Lu, Min ; Agarwal, Anika ; Anderson, Gray R ; Lin, Kevin H ; Winter, Peter S ; Cakir, Merve ; Wood, Kris C
Assuntos: Animals ; Anticancer properties ; Antineoplastic Agents, Phytogenic - pharmacology ; Antitumor agents ; Bcl-2 protein ; Bcl-x protein ; bcl-X Protein - metabolism ; Bridged Bicyclo Compounds, Heterocyclic - pharmacology ; Cancer ; Cell Line, Tumor ; Cell survival ; CRISPR ; Dependence ; Dose-Response Relationship, Drug ; Drug screening ; Gene expression ; Gene mapping ; Genes ; Inhibitors ; Male ; Mcl-1 protein ; Mice ; Neoplasms - metabolism ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; RNA, Messenger - metabolism ; Screening ; Sensitivity ; Sulfonamides - pharmacology
É parte de: Nature communications, 2018-08, Vol.9 (1), p.3513-13, Article 3513
Descrição: While inhibitors of BCL-2 family proteins (BH3 mimetics) have shown promise as anti-cancer agents, the various dependencies or co-dependencies of diverse cancers on BCL-2 genes remain poorly understood. Here we develop a drug screening approach to define the sensitivity of cancer cells from ten tissue types to all possible combinations of selective BCL-2, BCL-X , and MCL-1 inhibitors and discover that most cell lines depend on at least one combination for survival. We demonstrate that expression levels of BCL-2 genes predict single mimetic sensitivity, whereas EMT status predicts synergistic dependence on BCL-X +MCL-1. Lastly, we use a CRISPR/Cas9 screen to discover that BFL-1 and BCL-w promote resistance to all tested combinations of BCL-2, BCL-X , and MCL-1 inhibitors. Together, these results provide a roadmap for rationally targeting BCL-2 family dependencies in diverse human cancers and motivate the development of selective BFL-1 and BCL-w inhibitors to overcome intrinsic resistance to BH3 mimetics.
Editor: England: Nature Publishing Group
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Anterior Resultado 6 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

Systematic mapping of BCL-2 gene dependencies in cancer reveals molecular determinants of BH3 mimetic sensitivity

Soderquist, Ryan S ; Crawford, Lorin ; Liu, Esther ; Lu, Min ; Agarwal, Anika ; Anderson, Gray R ; Lin, Kevin H ; Winter, Peter S ; Cakir, Merve ; Wood, Kris C

England: Nature Publishing Group

Buscando em bases de dados remotas. Favor aguardar.