Imperial College London
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ProfessorAnneDell

Faculty of Natural Sciences, Department of Life Sciences

Professor of Carbohydrate Bichemistry
 
 
 
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a.dell

 
 
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Location

 

101BSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chakraborty:2023:10.1016/j.jid.2022.07.033,
author = {Chakraborty, A and Perez, M and Carroll, JD and Antonopoulos, A and Dell, A and Ortega, L and Mohammed, NBB and Wells, M and Staudinger, C and Griswold, A and Chandler, KB and Marrero, C and Jimenez, R and Tani, Y and Wilmott, JS and Thompson, JF and Wang, W and Sackstein, R and Scolyer, RA and Murphy, GF and Haslam, SM and Dimitroff, CJ},
doi = {10.1016/j.jid.2022.07.033},
journal = {J Invest Dermatol},
pages = {456--469.e8},
title = {Hypoxia Controls the Glycome Signature and Galectin-8-Ligand Axis to Promote Protumorigenic Properties of Metastatic Melanoma.},
url = {http://dx.doi.org/10.1016/j.jid.2022.07.033},
volume = {143},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The prognosis for patients with metastatic melanoma (MM) involving distant organs is grim, and treatment resistance is potentiated by tumor-initiating cells (TICs) that thrive under hypoxia. MM cells, including TICs, express a unique glycome featuring i-linear poly-N-acetyllactosamines through the loss of I-branching enzyme, β1,6 N-acetylglucosaminyltransferase 2. Whether hypoxia instructs MM TIC development by modulating the glycome signature remains unknown. In this study, we explored hypoxia-dependent alterations in MM glycomeassociated genes and found that β1,6 N-acetylglucosaminyltransferase 2 was downregulated and a galectin (Gal)-8-ligand axis, involving both extracellular and cell-intrinsic Gal-8, was induced. Low β1,6 N-acetylglucosaminyltransferase 2 levels correlated with poor patient outcomes, and patient serum samples were elevated for Gal-8. Depressed β1,6 N-acetylglucosaminyltransferase 2 in MM cells upregulated TIC marker, NGFR/CD271, whereas loss of MM cellintrinsic Gal-8 markedly lowered NGFR and reduced TIC activity in vivo. Extracellular Gal-8 bound preferentially to i-linear poly-N-acetyllactosamines on N-glycans of the TIC marker and prometastatic molecule CD44, among other receptors, and activated prosurvival factor protein kinase B. This study reveals the importance of hypoxia governing the MM glycome by enforcing i-linear poly-N-acetyllactosamine and Gal-8 expression. This mechanistic investigation also uncovers glycome-dependent regulation of pro-MM factor, NGFR, implicating i-linear poly-N-acetyllactosamine and Gal-8 as biomarkers and therapeutic targets of MM.
AU  - Chakraborty,A
AU  - Perez,M
AU  - Carroll,JD
AU  - Antonopoulos,A
AU  - Dell,A
AU  - Ortega,L
AU  - Mohammed,NBB
AU  - Wells,M
AU  - Staudinger,C
AU  - Griswold,A
AU  - Chandler,KB
AU  - Marrero,C
AU  - Jimenez,R
AU  - Tani,Y
AU  - Wilmott,JS
AU  - Thompson,JF
AU  - Wang,W
AU  - Sackstein,R
AU  - Scolyer,RA
AU  - Murphy,GF
AU  - Haslam,SM
AU  - Dimitroff,CJ
DO  - 10.1016/j.jid.2022.07.033
EP  - 469
PY  - 2023///
SP  - 456
TI  - Hypoxia Controls the Glycome Signature and Galectin-8-Ligand Axis to Promote Protumorigenic Properties of Metastatic Melanoma.
T2  - J Invest Dermatol
UR  - http://dx.doi.org/10.1016/j.jid.2022.07.033
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36174713
VL  - 143
ER  -
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