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Article Dans Une Revue Cancer Cell Année : 2015

Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth

C. Cheng
  • Fonction : Auteur
P. Ru
  • Fonction : Auteur
F. Geng
  • Fonction : Auteur
J. Liu
  • Fonction : Auteur
J. Y. Yoo
  • Fonction : Auteur
X. Wu
  • Fonction : Auteur
  • PersonId : 829304
X. Cheng
  • Fonction : Auteur
V. Euthine
P. Hu
  • Fonction : Auteur
J. Y. Guo
  • Fonction : Auteur
B. Kaur
  • Fonction : Auteur
A. Nohturfft
  • Fonction : Auteur
J. Ma
  • Fonction : Auteur
A. Chakravarti
  • Fonction : Auteur
D. Guo
  • Fonction : Auteur

Résumé

Tumorigenesis is associated with increased glucose consumption and lipogenesis, but how these pathways are interlinked is unclear. Here, we delineate a pathway in which EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound transcription factor with central roles in lipid metabolism. Glycosylation stabilizes SCAP and reduces its association with Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent proteolytic activation of SREBP. Xenograft studies reveal that blocking SCAP N-glycosylation ameliorates EGFRvIII-driven glioblastoma growth. Thus, SCAP acts as key glucose-responsive protein linking oncogenic signaling and fuel availability to SREBP-dependent lipogenesis. Targeting SCAP N-glycosylation may provide a promising means of treating malignancies and metabolic diseases.

Dates et versions

hal-01850543 , version 1 (27-07-2018)

Identifiants

Citer

C. Cheng, P. Ru, F. Geng, J. Liu, J. Y. Yoo, et al.. Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth. Cancer Cell, 2015, 28 (5), pp.569-81. ⟨10.1016/j.ccell.2015.09.021⟩. ⟨hal-01850543⟩
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