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Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.
Peng, Peng; Chavel, Colin; Liu, Wensheng; Carlson, Louise M; Cao, Sha; Utley, Adam; Olejniczak, Scott H; Lee, Kelvin P.
Afiliação
  • Peng P; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Chavel C; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Liu W; Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY, USA.
  • Carlson LM; Indiana University Simon Comprehensive Cancer Center, and the Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Cao S; Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Utley A; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Olejniczak SH; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Lee KP; Indiana University Simon Comprehensive Cancer Center, and the Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: kplee@iu.edu.
Cell Rep ; 43(7): 114445, 2024 Jul 23.
Article em En | MEDLINE | ID: mdl-38968073
ABSTRACT
Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Transdução de Sinais / Sobrevivência Celular / Mieloma Múltiplo Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Transdução de Sinais / Sobrevivência Celular / Mieloma Múltiplo Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos