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The role of stress inducible protein 1 (STI1) in the early embryonic vascular development and tumor angiogenesis


The cochaperone STI1 forms a protein complex with Hsp70 and 90 and that supports proper protein folding. STI1 is secreted associated to endosomal vesicles, once in extracelular space, it interacts with prion protein (PrPC) on plasma membrane and triggers several trophic effects, such as proliferation, protection against cell death, differentiation and migration. Such effects were observed in physiological (brain development and plasticity) and pathological (cancer and stroke) situations. STI1 ablation is lethal, promoting the death of embryos after implantation period. STI1 haploinsuficiency is associated with increased vulnerability to experimental ischemia. Hypoxia-driven STI1 secretion allows the interaction with PrPC triggering angiogenesis stimulation, this process is related to post-ischemia brain recovery. Together, this finding suggest the involvement of STI1-PrPC complex to the mechanisms which rules blood vessel formation. Thus, this project aims the study the participation of this complex in two situations: 1- during mouse development, associating the function to vascular precursors; 2 - in brain tumors, in which angiogenesis plays a fundamental role to tumor growth. This work will contribute to understand the functions of STI1 and its receptor PrPC in angiogenesis associated processes and, thus, the findings could be used to drug development. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SANTOS, TIAGO GOSS; MARTINS, VILMA REGINA; MAROSO HAJJ, GLAUCIA NOELI. Unconventional Secretion of Heat Shock Proteins in Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 5 MAY 2017. Web of Science Citations: 18.

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