PXD057634-1

PXD057634 is an original dataset announced via ProteomeXchange.

Title	ST6GAL1-driven sialyl-linkage switching in polarizing macrophages promotes formation of α2,6-sialylated nanotubes in anti-inflammatory cells
Description	Tumor-associated macrophages (TAMs) form functionally diverse populations of innate immune cells in the tumor microenvironment. While the pro- and anti-inflammatory TAMs are recognized to shape inflammation and impact disease progression in cancer, the molecular and cellular perturbations of the glycocalyx accompanying TAM polarization remain unknown. Taking a systems glycobiology approach, we here firstly used cell surface-focused glycomics and lectin flow cytometry of ex vivo polarized monocyte-derived macrophages to demonstrate profound sialyl linkage switching of the surface N-glycome in pro-inflammatory (α2,3-NeuAc-favored) and anti-inflammatory (α2,6-NeuAc-dominant) macrophages. No polarization-induced alterations in sialylation were observed in the surface O-glycome. Expression of ST6GAL1 that adds α2,6-sialylation to N-glycans was elevated in anti-inflammatory compared to levels in pro-inflammatory macrophages providing a mechanistic basis for the sialyl linkage switching which was supported by ST6GAL1 silencing. Interestingly, SNA-focused lectin cytochemistry of anti-inflammatory macrophages revealed dense networks of α2,6-sialylated nanotubules forming proteinaceous inter-connecting cellular structures that were absent in pro-inflammatory macrophages. Temporal ST6GAL1 silencing caused nanotubule fragmentation in the anti-inflammatory macrophages. Moreover, live cell recordings of anti-inflammatory macrophages cultured alone and with colorectal cancer (CRC) cells showed reduced macrophage motility and attenuated inter-macrophage and macrophage-CRC cell interactions upon ST6GAL1 disruption indicating functional roles of the α2,6-sialylated nanotubules. Finally, sialyl linkage switching was observed in pro- and anti-inflammatory TAMs using lectin histochemistry on tumor tissues from CRC patients with stage 4 disease. We report on the mechanistic basis for and functional consequences of the profound glycocalyx remodeling accompanying TAM polarization.
HostingRepository	PRIDE
AnnounceDate	2026-08-13
AnnouncementXML	Submission_2026-08-13_05:32:21.409.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Priya Dipta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-07 13:02:52	ID requested
⏵ 1	2026-08-13 05:32:21	announced

10.1101/2024.11.28.625934;

submitter keyword: ST6GAL1, macrophage, sialic acids, nanotubes, sialylation, colorectal cancer.

Morten Thaysen-Andersen
contact affiliation	Associate professor at Macquarie University, Sydney, Australia Visiting professor at Institute for Glyco-core Research (iGCORE), Nagoya Univeristy, Aichi, Japan
contact email	morten.andersen@mq.edu.au
lab head
Priya Dipta
contact affiliation	Student
contact email	priya.dipta@hdr.mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057634
     1. Label: PRIDE project
     2. Name: ST6GAL1-driven sialyl-linkage switching in polarizing macrophages promotes formation of α2,6-sialylated nanotubes in anti-inflammatory cells