Multilevel Proteomic Profiling of Colorectal Adenocarcinoma Caco-2 Cell Differentiation to Characterize an Intestinal Epithelial Model

Fekete, Emily Ef, Wang, Angela, Creskey, Marybeth, Cummings, Sarah E., Lavoie, Jessie R., Ning, Zhibin, Li, Jianjun, Figeys, Daniel, Chen, Rui and Zhang, Xu (2024) Multilevel Proteomic Profiling of Colorectal Adenocarcinoma Caco-2 Cell Differentiation to Characterize an Intestinal Epithelial Model. Journal of Proteome Research, 23 (7). pp. 2561-2575. ISSN 1535-3893

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Abstract

Emergent advancements on the role of the intestinal microbiome for human health and disease necessitate well-defined intestinal cellular models to study and rapidly assess host, microbiome, and drug interactions. Differentiated Caco-2 cell line is commonly utilized as an epithelial model for drug permeability studies and has more recently been utilized for investigating host-microbiome interactions. However, its suitability to study such interactions remains to be characterized. Here, we employed multilevel proteomics to demonstrate that both spontaneous and butyrate-induced Caco-2 differentiations displayed similar protein and pathway changes, including the downregulation of proteins related to translation and proliferation and upregulation of functions implicated in host-microbiome interactions, such as cell adhesion, tight junction, extracellular vesicles, and responses to stimuli. Lysine acetylomics revealed that histone protein acetylation levels were decreased along with cell differentiation, while the acetylation in proteins associated with mitochondrial functions was increased. This study also demonstrates that, compared to spontaneous differentiation methods, butyrate-containing medium accelerates Caco-2 differentiation, with earlier upregulation of proteins related to host-microbiome interactions, suggesting its superiority for assay development using this intestinal model. Altogether, this multiomics study emphasizes the controlled progression of Caco-2 differentiation toward a specialized intestinal epithelial-like cell and establishes its suitability for investigating the host-microbiome interactions.

Item Type:	Article
Additional Information:	All MS proteomics data that support the findings of this study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PDX049082, PDX049087, and PDX049091.
Uncontrolled Keywords:	caco-2,differentiation,intestinal cellular model,microbiome,proteomics,chemistry(all),biochemistry,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	09 Mar 2026 17:30
Last Modified:	15 Mar 2026 07:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102283
DOI:	10.1021/acs.jproteome.4c00276

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