Cell Signalling
PRINCIPAL INVESTIGATOR: Sonia Castillo-Lluva
GROUP MEMBERS
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Angélica Martínez López (Postdoctoral)
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Ana García Casas (Estudiante Tesis)
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Guiomar Infante Gutiérrez (Estudiante TFM)
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Manuel Fernández Fernández (Estudiante TFM)
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Nélida Salvador (Ayudante Investigación)
GENERAL RESEARCH OBJECTIVE OF THE GROUP
It is estimated that 1 in 8 women will be diagnosed with breast cancer (BC) during their lifetime, representing the most common female tumor. Most deaths associated with BC are due to metastasis invading organs like the bone, liver, lungs or brain. Moreover, a less aggressive subset of BCs, denominated estrogen-positive BC or luminal BC, can produce metastasis years or even decades after the primary tumor has been removed. The group is focused on the mechanisms responsible of cell polarity and cell migration, both necessary processes for the epithelial-mesenchymal transition (EMT). The EMT is a highly conserved cellular program that allows polarized, immotile epithelial cells to convert to motile mesenchymal cells. This important process has been implicated not only in physiological migration of cells, but also in the pathogenic program leading to carcinoma invasion and metastasis by giving rise to the dissemination of single carcinoma cells from primary epithelial tumors. The process of EMT is controlled by several proteins. Signalling pathways activated by intrinsic or extrinsic stimuli converge on these proteins and regulate the phenotypic changes of cancer cells. These EMT regulators may play an important role in cancer progression. Our group is focused on how the posttranslational modifications of these regulators are involved in migration and invasion of tumor cells. We have demonstrated that SUMOylation of the GTPase RAC1 was necessary for the invasion of breast cancer cells. Currently, we are interested in the implication of posttranslational modifications in tumor cell dissemination, as a new mechanism to inhibit and block metastasis. Furthermore, treated tumors that eventually relapse develop aggressive metastatic cancers and thus, recurrence constitutes an unresolved clinical problem that requires the development of effective anti-cancer therapies. Bidirectional communication between cells and their microenviron¬ment is critical for tumor initiation, progression and metastasis, complicating the already challenging task of treating cancer. New treatments directed against the tumor cells and their microenvironment can be considered a more realistic and effective therapeutic strategy. In this sense, we have recently published two regulators of the invasive program involve that influences the development of breast cancer by influencing tumor cells and the microenvironment landscape. Thus, we pretend to identify new effectors and therapeutic strategies that directly target the primary tumor and its tumor microenvironment to inhibit metastasis in BC.
LINES OF THE RESEARCH GROUP AND RESPONSIBLE RESEARCHER
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1- Role of posttranslational modification in metastasis (PI: Sonia Castillo-Lluva)
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2- Tumor microenvironment modification as a strategy to prevent metastasis (PI:Sonia Castillo-Lluva)