Biology subjects

Signoret, N.

Publications and source records attributed to Signoret, N..

3 recordsLinked to original sources

bioRxiv2026

Characterisation of prostate cancer sialome re-engineering via CMAH transfection reveals a bystander effect that propagates Neu5Gc presentation to neighbouring cells

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.

cancer biology↗

bioRxiv2025

The Androgen Receptor and MYC synergise to modulate the synthesis of Siglec-7 ligands in prostate cancer

Glyco-immune checkpoints have recently been shown to be critical mediators of immunotherapy resistance across multiple cancer types. In clinical trials, immunotherapeutic treatments for prostate cancer have failed to elicit durable clinical responses. PCa progression is driven by transcriptional networks regulated by key transcription factors including the androgen receptor (AR) and the oncogene MYC. How this crossover between hormone and oncogene-driven signalling pathways regulates tumour glyco-immune checkpoints remains unclear. Here, we show that O-glycans are the major substrates for sialylation in prostate cancer and that sialyltransferases that have preferences for O-glycans are differentially regulated by androgens. We show that supraphysiological levels of androgens produce distinct glycopeptide profiles in prostate cancer cells compared with cells exposed to physiological androgens. Additionally, we identify a direct and coordinated role for AR and MYC in regulating ST3Gal1 and the synthesis of Siglec-7 ligands in prostate cancer. Both transcription factors converge to repress ST3GAL1, thereby limiting the generation of Siglec-7 ligands. These findings highlight a context-dependent, cooperative relationship between the AR and MYC in shaping the tumour sialome, linking hormonal signalling and oncogenic transcription to Siglec biology. Our study highlights how cell-type specific differences in transcriptional networks has important downstream effects for immune modulating glycans and has tumour specific clinical implications.

cancer biology↗

bioRxiv2022

Super-resolved imaging deciphers ligand dependent membrane behaviour of the onco-immunogenic CCR5 receptor.

The ability of tumors to establish a pro-tumorigenic microenvironment is becoming an important point of investigation in the search for new therapeutics. Tumors form microenvironments in part by the education of immune cells attracted via chemotactic axes such as that of CCR5-CCL5. Further, CCR5 upregulation by cancer cells, coupled with its association with pro-tumorigenic features such as drug-resistance and metastasis, has suggested CCR5 as a target for therapeutic inhibition. However, with several conformational "pools" being reported, phenotypic investigations must be capable of unveiling heterogeneity. Addressing this challenge, we performed structured illumination (SIM) and Partially TIRF coupled HILO (PaTCH) microscopy for super-resolution imaging and single-molecule imaging of CCR5 in fixed cells. Determining the positions of super-resolved CCR5 assemblies revealed a non-random spatial orientation. Further, intensity-tracking of assemblies revealed a distribution of molecular stoichiometries indicative of dimeric sub-units independent of CCL5 perturbation. These biophysical methods can provide important insights into the structure and function of onco-immunogenic receptors and a plethora of other biomolecules. HighlightsO_LIWe use SIM and novel PaTCH microscopy for precise bioimaging and single-molecule tracking of receptor protein CCR5 in model cell line C_LIO_LIBy tracking the position of CCR5 assemblies we conclude that they are clustered in the plasma membrane beyond a level expected from a random distribution C_LIO_LIWe use these high-precision data to determine molecular stoichiometries of CCR5 assemblies C_LI

biophysics↗