Dataset Information

Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse

ABSTRACT: Colorectal cancer molecular signatures derived from omics data can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease relapse are currently lacking. Here, we present a comprehensive multi-omics analysis of a Danish colorectal cancer tumor cohort composed of 412 biopsies from tumors of 371 patients diagnosed at TNM stage II or III. From mass spectrometry-based patient proteome profiles, we classified the tumors into four molecular subtypes, including a mesenchymal-like subtype. As the mesenchymal-rich tumors are known to represent the most invasive and metastatic phenotype, we focused on the protein signature defining this subtype to evaluate their potential as relapse risk markers. Among signature-specific proteins, we followed-up Caveolae-Associated Protein-1 (CAVIN1) and demonstrated its role in tumor progression in a 3D in vitro model of colorectal cancer. Compared to previous omics analyses of CRC, our multi-omics classification provided deeper insights into EMT in cancer cells with stronger correlations with risk of relapse.

INSTRUMENT(S): Orbitrap Astral

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Colon Endothelium

DISEASE(S): Colon Cancer

SUBMITTER: Leander Van der Hoeven

LAB HEAD: Jesper Velgaard Olsen

PROVIDER: PXD056331 | Pride | 2025-03-17

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20230501_EXPL1_Evo3_LH_30SPD_DIA_15k2s_HT29_Sph_6h_R1.raw	Raw
	20230501_EXPL1_Evo3_LH_30SPD_DIA_15k2s_HT29_Sph_6h_R2.raw	Raw
	20230501_EXPL1_Evo3_LH_30SPD_DIA_15k2s_HT29_Sph_6h_R3.raw	Raw
	20230501_EXPL1_Evo3_LH_30SPD_DIA_15k2s_HT29_Sph_Ctrl_R1.raw	Raw
	20230501_EXPL1_Evo3_LH_30SPD_DIA_15k2s_HT29_Sph_Ctrl_R2.raw	Raw

Items per page:

1 - 5 of 36

Similar Datasets

Project description:Among all cancers, colorectal cancer (CRC) is the 3rd most common and the 2nd leading cause of death worldwide. New therapeutic strategies are required to target cancer stem cells (CSCs), a subset of tumor cells highly resistant to present-day therapy and responsible for tumor relapse. CSCs display dynamic genetic and epigenetic alterations that allow quick adaptations to perturbations. Lysine-specific histone demethylase 1A (KDM1A), a FAD-dependent H3K4me1/2 and H3K9me1/2 demethylase, was found to be upregulated in several tumors and associated with a poor prognosis due to its ability to maintain CSCs staminal features. Here, we explored the potential role of KDM1A targeting in CRC by characterizing the effect of KDM1A silencing in differentiated and CRC stem cells (CRC-SCs). In CRC primary samples, KDM1A expression was associated with a worse prognosis, confirming its role as an independent negative prognostic factor of CRC. Consistently, biological assays such as methylcellulose colony formation, invasion, and migration assays demonstrated a significantly decreased self-renewal potential, as well as migration and invasion potential upon KDM1A silencing. Our untargeted omics approach (transcriptomic and proteomic) revealed the association of KDM1A silencing with CRC-SCs cytoskeletal and metabolism remodeling towards a differentiated phenotype (e.g., the activation of a collateral mitochondrial metabolic pathway independent from succinate-CoA ligase GDP-forming subunit beta 2, expressions of brush border’s protein villin, and ketogenic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2) suggesting a key role of KDM1A in cell metabolism. Also, KDM1A silencing resulted in a 3-fold increase in the expression of miR-506-3p. Lastly, loss of KDM1A markedly reduced 53BP1 DNA repair foci, implying the involvement of KDM1A in the DNA damage response. Overall, our results indicate that KDM1A plays a key role in CRC progression and therefore it represents a promising epigenetic target to prevent tumor relapse.

Dataset Information

Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets