Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism.

Autor: Linzer RW; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Guida DL; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Aminov J; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Snider JM; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Khalife G; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Buyukbayraktar AB; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Alhaddad C; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Resnick AE; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Wang P; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Pan CH; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Allopenna JJ; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA., Clarke CJ; Department of Medicine and the Cancer Center, Stony Brook University, Stony Brook, NY, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2022 Oct; Vol. 36 (10), pp. e22558.
DOI: 10.1096/fj.202200748R
Abstrakt: Oncogenic reprogramming of cellular metabolism is a hallmark of many cancers, but our mechanistic understanding of how such dysregulation is linked to tumor behavior remains poor. In this study, we have identified dihydroceramide desaturase (DES1)-which catalyzes the last step in de novo sphingolipid synthesis-as necessary for the acquisition of anchorage-independent survival (AIS), a key cancer enabling biology, and establish DES1 as a downstream effector of HER2-driven glucose uptake and metabolism. We further show that DES1 is sufficient to drive AIS and in vitro tumorigenicity and that increased DES1 levels-found in a third of HER2+ breast cancers-are associated with worse survival outcomes. Taken together, our findings reveal a novel pro-tumor role for DES1 as a transducer of HER2-driven glucose metabolic signals and provide evidence that targeting DES1 is an effective approach for overcoming AIS. Results further suggest that DES1 may have utility as a biomarker of aggressive and metastasis-prone HER2+ breast cancer.
(© 2022 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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