We study molecular and cellular mechanisms involved during the dynamic regulation of cell plasticity and how the tumor microenvironment regulates the expression of key genes in this process. Cell plasticity in tumors contributes to the heterogeneous cell population observed in tumors, and consequently, their recurrence after treatment and dissemination.
Cancer Stem Cells (CSC) are those tumor cells responsible for cell plasticity and express core pluripotency factors and epigenetic regulators leading to the acquisition/maintenance of a malignant cell phenotype.
Also, TGF-beta family of proteins, as part of the tumor microenvironment and active in tumors, contribute to the maintenance of the stem-like properties.
Our research includes the use of human tumor samples and mouse xenograft models, and three-dimensional (3D) cultures of cancer cells (enrichment of CSC) that simulate in vitro the conditions of cell plasticity in the tumor. To conceive and understand the organization and dynamic progression of tumor cells in these models, we carried out a multidisciplinary approach and advanced microscopy methods.
Publications related to this project
- Muñoz-Bernart M*, Budnik N*, Castro A, Manzi M, Monge ME, Pioli J, Defranchi S, Parrilla G, Santilli JP, Davies K, Espinosa JM, Kobayashi K, Vigliano C, Perez-Castro C.
S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity.
Biol Direct 18: 8 (2023)
* Contributed equally
- Vera M.B., Morris-Hanon O., Nogueiras G.I., Ripari L.B., Esquivel M.I., Perez-Castro C., Romorini L., Sevlever G.E., Scassa M.E., Videla-Richardson G.A.
Noxa and Mcl-1 expression influence the sensitivity to BH3-mimetics that target Bcl-xL in patient-derived glioma stem cells.
Sci Rep. 12:17729 (2022).
- Cuenca, M.B., Canedo, L., Perez-Castro, C*., Grecco, H.E*.
An Integrative and Modular Framework to Recapitulate Emergent Behavior in Cell Migration.
Frontiers in Cell and Developmental Biology, 8: 615759 (2020).
- Thomas, L., Florio, T., Perez-Castro, C.
Extracellular Vesicles Loaded miRNAs as Potential Modulators Shared Between Glioblastoma, and Parkinson’s and Alzheimer’s Diseases.
Frontiers in Cellular Neuroscience 14: 590034 (2020).
- Ferreyra Solari NE, Belforte FS, Canedo L, Videla-Richardson GA, Espinosa JM, Rossi M, Serna E, Riudavets MA, Martinetto H, Sevlever G and Perez-Castro C.
The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem–like Properties in Glioblastoma That Contribute to Tumorigenesis.
Cancer Research 76: 5383-5394 (2016).
- Parra, R.G.; Rohr, C.O.; Koile, D.; Perez-Castro, C.; Yankilevich, P.
INSECT 2.0: a web-server for genome-wide cis-regulatory modules prediction.
Bioinformatics 32:1229-31 (2016).
- Rohr, C.O.; Parra, R.G.;Yankilevich, P*.;Perez Castro, C*.
INSECT: In silico search for co-occurring transcription factors.
Bioinformatics 29:2852-2858 (2013).
- Perez Castro, C.; Renner, U.; Haedo, M.; Gunter, K.; Stalla, G.K.; Arzt, E.
Cellular and Molecular Specificity of Pituitary Gland Physiology.
Physiological Reviews 92:1-38 (2012)
- Perez-Castro, C., Piscopo, D, Nakagawa, T, Derynck, R.
Cornichon regulates transport and secretion of TGF-alpha related proteins in metazoan cells.
Journal of Cell Science 120:2454-2466 (2007).