Research
Nuclear signaling and cancer : V. Cavaillès

Our main objective is to decipher the transcriptional networks controlling the expression of key genes linked to cellular homeostasis and their deregulation in cancer. Our research focuses on transcriptional coregulators, as well as oncogenic signaling pathways, notably those of nuclear receptors. We study the deregulation of various biological processes, such as cell growth, tumor metabolism, genome stability and the immune microenvironment. At the same time, we are collaborating with chemists to develop new biomaterials to treat various bone tumor pathologies. Expected results include a better understanding of the mechanisms.

Axis 1 : Transcription networks in breast cancers
(S Jalaguier, CRCN INSERM)
We previously characterized the role of the RIP140/LCoR complex (Jalaguier et al, Oncogene 2017) and identified IFNγ signaling as a major target of RIP140 in breast cancer (Jalaguier et al., Int J Cancer 2025). More recently, we hypothesized that relocalization of the vitamin D receptor (VDR) in triple-negative breast cancer (TNBC) could restore its protective activity. We will use a VDR agonist and inhibition of exportins, to study their effects on VDR-responsive genes and on TNBC cell proliferation, with transcriptome analysis to uncover signaling pathways for targeted therapy. 

Axis 2 : Hypoxia-mediated secretion of extracellular vesicles in cancer-associated cachexia 
(C Teyssier, CRHC INSERM)
Hypoxia facilitates intercellular communication, with extracellular vesicles (EVs) playing a crucial role by transferring biological material between tumor and distant cells. EVs could participate in the metabolic reprogramming that affects distant tissues, such as skeletal muscles. This process is known as cancer cachexia and impacts quality of life and treatment response. Our project aims to detect different RIP140 forms in EVs from colorectal cancer cells and study their impact on muscle metabolism, demonstrating that wild-type or mutated RIP140 influences the metabolism of distant tissues and contributes to cancer-associated cachexia.

Axis 3: Regulation of tumor immune microenvironment in colorectal cancers 
(A Castet-Nicolas MCU-PH - V Cavaillès DR1 CNRS)
The anti-tumor immune response is crucial in the development of gastro-intestinal cancers (GIC), with a high rate of therapeutic escape. Our unpublished data suggest that RIP140 controls the immune response in colorectal cancer (CRC). This research aims to demonstrate the role of RIP140 in restructuring the tumor immune microenvironment (TIME) and its resistance to chemo/immunotherapies. Using genetically modified mouse models and human tumor biopsies, we will clarify its role and assess its potential as a predictive marker for therapy response. In parallel, we have initiated a project on the impact of PFAS eternal pollutants on intestinal tumorigenesis.

Axis 4: New biomaterials for the treatment of bone cancers 
(V Cavaillès, DR1 CNRS)
In this axis, we are developing translational and interdisciplinary projects in collaboration with chemists from the IEMM in Montpellier and with clinicians. Our goal is to develop new biomaterials such as 3D scaffolds and injectable cements for the local administration of drugs, which will improve the treatment of different pathologies, including bone tumors such as osteoclastoma or breast cancer metastases. Part of this work is developed through a partnership with a start-up company.