bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.04.03.647001

Integrated tumour-immune cell response modelling of Luminal A breast cancer details malignant signalling and ST3Gal1 inhibitor induced reversal

Kaya, H. E.·Naidoo, K. J.
View original source ↗Export metadata ↓

Abstract

Aberrant O-glycosylation of mucin-type glycopeptide 1 (MUC1) is implicated in cancerous cellular processes involving the manipulation of immune response to favour tumour growth and metastasis. There is an unmet need for systems glycobiology models to probe the relationship between MUC1 O-glycosylation and immune cells within the tumour microenvironment. We expand on the sparsely understood MUC1 and immune cell interactions by building a complete systems model that combines the glycosylation network in the tumour cell with downstream biological networks. An ordinary differential equations- based model of the effect of aberrant glycosylation on immune modulation in breast cancer was constructed. The model comprises three interdependent component models that are MUC1-type O-glycosylation in the tumour cell, chemokine secretion in macrophages, and signal transduction in the tumour cells. A comparative CytoCopasi algorithm was developed to sequentially perturb the networks by an aberrant O-glycosylation. Comparative simulations revealed that upregulation of tumour-associated MUC1 sialyl-T antigen in Luminal A breast cancer stimulated the upregulation of the chemokine CXCL5 in tumour-associated macrophages. Consequently, increased CXCL5 binding by the tumour cell led to a positive feedback loop through overactive signal transduction and autocrine CXCL5 production. Finally, perturbing the glycosylation network with the sialyltransferase inhibitor Soyasaponin-I abrogated the cancerous upregulations in the downstream networks.

Source connections

Explore related subjects

systems biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kaya, H. E., Naidoo, K. J.. 2025-04-07. Integrated tumour-immune cell response modelling of Luminal A breast cancer details malignant signalling and ST3Gal1 inhibitor induced reversal. https://doi.org/10.1101/2025.04.03.647001

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Limit-pushing overexpression reveals constraints on protein abundance

Proteins are often classified as toxic or non-toxic without measuring the abundance reached, leaving constraints on tolerable protein abundance unresolved. We established a limit-pushing approach in Saccharomyces cerevisiae combining strong inducible expression with gTOW-mediated high-copy selection to counteract copy-number compensation while measuring protein abundance and growth. Nearly all of approximately 80 chromosome I proteins severely inhibited growth or reduced viability at sufficiently high abundance. We established IE50, the expression level associated with a 50% reduction in growth rate, to quantify their widely varying overexpression tolerance. IE50 was positively associated with predicted structural order and cytoplasmic localization propensity and negatively associated with sulphur content. Single-cell imaging linked higher tolerance to proteins remaining cytoplasmic without becoming aggregation-positive and revealed abundance-dependent changes in localization and organelle morphology. At extreme abundance, Fun12, Nup60, and Pex22 generated distinct large-scale intracellular states through specific sequence regions. These findings establish overexpression toxicity as a quantitative property linked to protein characteristics and reveal both constraints on tolerable abundance and sequence-dependent capacities for intracellular organization.

systems biology↗
bioRxiv2026

Accessing Enzyme Kinetic Data and Prediction Methods at Scale

Enzyme kinetic parameters inform metabolic models, yet experimental measurements are sparse. A growing body of work predicts them from protein and substrate features, but software fragmentation hinders adoption, so downstream tools lock into the most accessible method. We present OpenKinetics Predictor (at predictor.openkinetics.org), an open-source platform integrating thirteen methods in isolated environments behind one interface. The platform optionally reports similarity between query proteins and each method's training data to contextualise reliability. A common featurisation-prediction abstraction keeps it extensible, and independent parties, including original authors, contributed many methods. We pair it with a data portal (at data.openkinetics.org) that exposes CatLog, a curated kinetic dataset, with precomputed embeddings, predicted binding sites, and standardised splits. Both offer a web interface and an API, and the GECKO modelling toolbox already calls the predictor API. As a case study, we predict across an E. coli model and find inter-predictor agreement varies with metabolic context and data availability.

systems biology↗
bioRxiv2026

A thermoregulatory design principle for transitions into hypometabolism

Mammals entering torpor or hibernation undergo an abrupt transition from normothermia to hypothermia, yet how thermoregulation enables this switch remains poorly understood. Here, we identify dynamical signatures that precede these transitions and a mathematical principle that can generate them. In fasting-induced torpor in mice, body-temperature fluctuations increased before torpor onset, providing an early-warning signal that tracked proximity to the transition better than temperature decline alone. A heat-balance model showed that reducing how strongly the effective heat-loss coefficient depends on body temperature reorganizes thermoregulatory stability, allowing a low-temperature equilibrium to emerge while the normothermic state remains stable. This organization is consistent with a symmetry-broken pitchfork involving a saddle-node. Similar increases in temperature fluctuations preceded hibernation onset in hamsters. These findings link pre-transition temperature dynamics to changes in the underlying thermoregulatory landscape and provide a framework for detecting and understanding transitions from normothermia to hypothermia.

systems biology↗