Journal
LIFE SCIENCE ALLIANCE
Volume 5, Issue 7, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202101334
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Funding
- la Ligue Nationale Contre le Cancer [R18159CC]
- Institut National du Cancer [7981]
- Rennes Metropole [R20167NN]
- Agence Nationale de la Recherche [ANR-10-INBS-08]
- GRAL, a program from the Chemistry Biology Health Graduate School of University Grenoble Alpes [ANR-17-EURE-0003]
- Ligue Nationale Contre le Cancer
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The glucose-requiring hexosamine biosynthetic pathway (HBP) and the coat complex II (COPII) play a crucial role in the survival of lung adenocarcinoma (LUAD) cells in low glucose conditions. Up-regulation of HBP resists the production of abnormal proteins induced by low glucose, while up-regulation of COPII restores the cell surface expression of certain glycoproteins.
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 micro-environments, 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.
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