CRP2, an innovative target for metastatic breast cancer, with multiple rolesin the tumour and tumour microenvironmen

Project Details


Development of metastases is the primary cause of death for most cancers.Cancer-associated fibroblasts (CAFs) are key contributors to this process,promoting remodeling of the tumour microenvironment (TME). Thisfacilitates cancer cell invasion and escape from the primary tumour.Invadopodia are actin-rich membrane structures that are essential indegradation of the extracellular matrix during TME remodeling and cancercell invasion. We have accumulated convincing evidence that CRP2, acytoskeletal regulatory protein associated with significantly worse overalland distant metastasis-free survival in breast cancer, critically promotesbreast cancer cell invadopodial function through two distinct mechanisms:formation and stabilization of invadopodia, and transcriptional induction ofpro-metastatic matrix metalloproteinases. Interestingly, we also observedthe presence of CRP2 in CAFs in human breast cancer samples andactivated fibroblasts. Additionally, it has been previously reported that CRP2is a potent co-factor in differentiation of -smooth muscle actin (SMA)+smooth muscle cells. Therefore, the CRP2-TME project aims to establishthe role of CRP2 in SMA+ CAF activation and function in clinically relevantin vivo models, and to characterise the mechanism through which CRP2 inCAFs contributes to metastatic dissemination of breast cancer cells.Furthermore, we will analyse the prevalence and clinical significance ofCRP2 in the stromal compartment. Altogether, we aim to solidify thetherapeutic rationale of targeting CRP2 in metastatic breast cancer, as asingle protein working in both stromal and cancer cells to regulate the actincytoskeleton, a hitherto unexploited target in cancer therapy.
Effective start/end date1/01/2031/12/21


  • FNRS - Fonds National de la Recherche Scientifique: €148,345.00


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