CXCR4/ACKR3/GRK2-governed networks in cancer cell migration and metastasis
Early stage researcher 13 (ESR13) project
Supervision: Prof. Dr. Federico Mayor Jr., Prof. Dr. Petronila Penela
I - Project proposal:
- Investigate signalling network signatures (phosho-protein barcodes, signalling pathways, cell acetylome, secretome) upon CXCL12-induced migration and proliferation via CXCR4 and/or ACKR3 in model breast and colon cancer cell lines. Influence of GRK2 dosage and of co-stimulation of relevant RTK and modulation by small molecule inhibitors or CXCR4/ACKR3, RTK nanobodies.
- Analyse effects of CXCR4/ACKR3/GRK2 inhibition (via nanobodies, small molecule inhibitors) on in vivo metastatic potential of breast cancer cells or colon cancer Cell signalling techniques, Co-ip and confocal microscopy in cell models, 2D and 3D migration/invasion assays, XCell-based adhesion and proliferation assays, in vivo tumor models in mice
Cell signalling techniques, Co-ip and confocal microscopy in cell models, 2D and 3D migration/invasion assays, XCell-based adhesion and proliferation assays, in vivo tumor models in mice
Universitätsklinikum Jena – Use of sensors to investigate early events in GRK2 and beta-arrestin dynamics/recruitment upon CXCL12-induced CXCR4 and/or ACKR3 receptor activation in model HEK293 cells
Vrije Universiteit Amsterdam – Validate use CXCR4/ACKR3 nanobodies for in vivo use
II - Requirement candidate:
Required diploma: MSc degree in molecular/biomedical Life Sciences, Pharmaceutical Sciences or related Life Sciences degree.
Required expertise: cell culture, cell-based assays, biochemistry, molecular biology.
Recommended expertise: GPCR signalling, confocal microscopy, migration and proliferation assays, in vivo murine cancer models
- Penela, P., Ribas, C., SánchezMadrid, F., Mayor, F.Jr. G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub. Cell Mol Life Sci. 2019 Aug 20. doi: 10.1007/s00018-019-03274-3. (Epub ahead of print)
- Neves M, Fumagalli A, van den Bor J, Marin P, Smit MJ, Mayor F Jr. The role of ACKR3 in breast, lung and brain cancer. Mol. Pharmacol 2019, pii: mol.118.115279.
- Nogués L, Palacios-García J, Reglero C, Rivas V, Neves M, Ribas C, Penela P, Mayor F Jr. G protein-coupled receptor kinases (GRKs) in tumorigenesis and cancer progression: GPCR regulators and signaling hubs. Semin Cancer Biol. 48:70-90 (2018)
- Nogués L, Reglero C, Rivas V, Salcedo A, Lafarga V, Neves M, Ramos P, Mendiola M, Berjón A, Stamatakis K, Zhou XZ, Lu KP, Hardisson D, Mayor F *, Penela P* (*, corresponding authors). G Protein-coupled Receptor Kinase 2 (GRK2) Promotes Breast Tumorigenesis Through a HDAC6-Pin1 Axis. EBioMedicine.13:132-145 (2016)
Rivas V, Carmona R, Muñoz-Chápuli R, Mendiola M, Nogués L, Reglero C, Miguel-Martín M, García-Escudero R, Dorn GW 2nd, Hardisson D, Mayor F Jr *, Penela P * (*, corresponding authors). Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2. J Clin Invest. 123,4714-30 (2013)
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Include in heading - ONCORNET2.0 + ESR#