Characterisation of prostate cancer sialome re-engineering via CMAH transfection reveals a bystander effect that propagates Neu5Gc presentation to neighbouring cells
- 1University of York
Abstract
Sialic acids are a family of nine-carbon -keto sugars that play essential roles in human health and disease. In mammals, they are found in two main forms: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), with interactions between Neu5Ac-containing glycans and Siglec receptors on immune cells increasingly recognised as glyco-immune checkpoints, promoting immunosuppression. However, humans do not synthesise Neu5Gc due pseudogenisation of the CMAH gene which encodes the cytidine monophospho-N-acetylneuraminic acid hydroxylase enzyme responsible for CMP-Neu5Ac conversion into CMP-Neu5Gc, which then serves as the donor substrate for sialyltransferases. Here, we investigated the effects of re-engineering tumour cell-surface glycans in a prostate cancer cell model by expressing rat CMAH, thereby enabling the conversion of CMP-Neu5Ac to CMP-Neu5Gc. LNCaP cells transfected with the rat CMAH gene predominantly incorporated Neu5Gc into mucin-associated O-glycans implicated in immune suppression. Treatment with sialidase significantly reduced Neu5Gc expression, indicating that Neu5Gc was presented on cell-surface glycans, while cell-tracing experiments demonstrated the transfer of Neu5Gc to neighbouring cells, revealing a potential bystander effect capable of propagating Neu5Gc expression within the tumour microenvironment.
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BibTeX
@misc{uno2026characterisation,
title = {{Characterisation of prostate cancer sialome re-engineering via CMAH transfection reveals a bystander effect that propagates Neu5Gc presentation to neighbouring cells}},
author = {Y. Uno and A. Noble and E. Hutton and N. Signoret and M. Fascione},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.750340},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750340v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Characterisation of prostate cancer sialome re-engineering via CMAH transfection reveals a bystander effect that propagates Neu5Gc presentation to neighbouring cells
AU - Y. Uno
AU - A. Noble
AU - E. Hutton
AU - N. Signoret
AU - M. Fascione
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.750340
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.750340v1
AB - Sialic acids are a family of nine-carbon -keto sugars that play essential roles in human health and disease. In mammals, they are found in two main forms: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), with interactions between Neu5Ac-containing glycans and Siglec receptors on immune cells increasingly recognised as glyco-immune checkpoints, promoting immunosuppression. However, humans do not synthesise Neu5Gc due pseudogenisation of the CMAH gene which encodes the cytidine monophospho-N-acetylneuraminic acid hydroxylase enzyme responsible for CMP-Neu5Ac conversion into CMP-Neu5Gc, which then serves as the donor substrate for sialyltransferases. Here, we investigated the effects of re-engineering tumour cell-surface glycans in a prostate cancer cell model by expressing rat CMAH, thereby enabling the conversion of CMP-Neu5Ac to CMP-Neu5Gc. LNCaP cells transfected with the rat CMAH gene predominantly incorporated Neu5Gc into mucin-associated O-glycans implicated in immune suppression. Treatment with sialidase significantly reduced Neu5Gc expression, indicating that Neu5Gc was presented on cell-surface glycans, while cell-tracing experiments demonstrated the transfer of Neu5Gc to neighbouring cells, revealing a potential bystander effect capable of propagating Neu5Gc expression within the tumour microenvironment.
ER -