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Article Dans Une Revue Life Science Alliance Année : 2022

The hexosamine pathway and coat complex II promote malignant adaptation to nutrient scarcity

Sabine Brugière
  • Fonction : Auteur
Yohann Couté
Justine Rudewicz
Toufic Renno

Résumé

The glucose-requiring hexosamine biosynthetic pathway (HBP), which produces UDP-N-acetylglucosamine for glycosylation reactions, promotes lung adenocarcinoma (LUAD) progression. However, lung tumor cells often reside in low-nutrient microenvironments, and whether the HBP is involved in the adaptation of LUAD to nutrient stress is unknown. Here, we show that the HBP and the coat complex II (COPII) play a key role in cell survival during glucose shortage. HBP up-regulation withstood low glucose-induced production of proteins bearing truncated N-glycans, in the endoplasmic reticulum. This function for the HBP, alongside COPII up-regulation, rescued cell surface expression of a subset of glycoproteins. Those included the epidermal growth factor receptor (EGFR), allowing an EGFR-dependent cell survival under low glucose in anchorage-independent growth. Accordingly, high expression of the HBP rate-limiting enzyme GFAT1 was associated with wild-type EGFR activation in LUAD patient samples. Notably, HBP and COPII up-regulation distinguished LUAD from the lung squamous-cell carcinoma subtype, thus uncovering adaptive mechanisms of LUAD to their harsh microenvironment.

Domaines

Cancer
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Dates et versions

hal-03660129 , version 1 (05-05-2022)

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Helena Dragic, Audrey Barthelaix, Cédric Duret, Simon Le Goupil, Hadrien Laprade, et al.. The hexosamine pathway and coat complex II promote malignant adaptation to nutrient scarcity. Life Science Alliance, 2022, 5 (7), pp.e202101334. ⟨10.26508/lsa.202101334⟩. ⟨hal-03660129⟩
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