Multi-omics of colon tumor progression organoids reveals putative mediators of colorectal cancer metastasis
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ABSTRACT:
PROVIDER: PRJNA870314 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21101616_1.fastq.gz | Fastqsanger.gz | |||
| SRR21101616_2.fastq.gz | Fastqsanger.gz | |||
| SRR21101617_1.fastq.gz | Fastqsanger.gz | |||
| SRR21101617_2.fastq.gz | Fastqsanger.gz | |||
| SRR21101618_1.fastq.gz | Fastqsanger.gz |
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Project description:The development of metastasis severely reduces the life expectancy of patients with colorectal cancer (CRC). Loss of SMAD4 is a key event in late-stage CRC resulting in the progression to metastatic CRC in 10-30% of the cases. However, the biological processes and underlying molecular mechanisms that it affects are not fully understood. Here, we applied a multi-omics approach to a CRC tumor progression organoid model that faithfully reflects the metastasis-inducing effects of SMAD4 inactivation. We show that loss of SMAD4 results in loss of differentiation and activation of pro-migratory and cell proliferation processes, which is accompanied by the disruption of several key oncogenic pathways, including the TGFB, WNT, and VEGF pathways. In addition, SMAD4 inactivation leads to increased secretion of proteins that are known to be involved in a variety of pro-metastatic processes. Finally, we show that one of the factors that is specifically secreted by metastatic organoids – DKK3 – reduces the anti-tumor effects of natural killer cells (NKCs). Altogether, our data provides promising new targets concerning the role of SMAD4 perturbation and metastatic disease in CRC.
2022-12-11 | PXD036441 | Pride
Project description:The pathogenesis of Colorectal cancer (CRC) metastasis remains unclear.We collect clinical data from our center and use Integrative omics to analyze and predict candidate biomarkers of colorectal cancer and distant metastasis.
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