Project description
Uncovering a hidden driver of colorectal cancer
Colorectal cancer (CRC) is one of the deadliest cancers worldwide, with many patients facing poor outcomes due to metastasis. Cancer progression is strongly influenced by cancer-associated fibroblasts (CAFs), which alter the tumour’s environment to support growth and evade the immune system. Hypoxia, or low oxygen levels, is common in advanced tumours and activates HIF-1α, a protein that helps cancer cells survive harsh conditions. While much is known about HIF-1α in cancer cells, its role in CAFs remains unclear. Supported by the Marie Skłodowska-Curie Actions programme, the HifCAT project explores how HIF-1α affects CAFs in CRC. The aim is to uncover how CAFs drive tumour progression and metastasis, ultimately paving the way for better treatments.
Objective
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite significant advancements in understanding CRC pathogenesis, the clinical prognosis of CRC patients is still poor due to metastasis dissemination. Cancer progression is often associated with the presence of cancer-associated fibroblasts (CAFs) in the tumor microenvironment that regulate processes such as extracellular matrix (ECM) deposition and repression of the immune response. The establishment of a hypoxic environment and activation of its main effector, the hypoxia-inducible factor-1α (HIF-1α), are common features of advanced cancers. HIF-1α is a transcription factor, which regulates several genes that are exploited by tumor cells to escape from a nutrient-deprived environment and to survive as well as resist to treatment. However, the role of HIF-1α in CAFs has not be addressed so far in CRC. This research seeks to elucidate the effects of hypoxia on different aspects of CAFs' function , using in vitro functional assays and innovative co-culture models with patient-derived CAFs and matching tumor organoids. Furthermore, the study aims to unveil the role of HIF-1α expression in CAFs during tumor initiation and progression using a colitis-associated carcinogenesis model and pinpoint the origin of HIF-1α+ CAFs employing a lineage tracing model. Finally, in silico analysis of scRNAseq data will allow to detect the subset of CAFs that are responsive to hypoxia in different stages of carcinogenesis and in metastatic dissemination. Overall, this project will study the unappreciated role of HIF-1α in CAFs in the context of CRC with the ultimate goal to pave the way to new therapeutic strategies.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
4365 ESCH-SUR-ALZETTE
Luxembourg