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ADAM23 signaling in glioblastomas and its role in Wnt pathway control

Grant number: 16/06857-9
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2016
Effective date (End): June 30, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Erico Tosoni Costa
Grantee:Elisa Helena Farias Jandrey
Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Glioblastoma Multiform (GBM) is the most common and lethal human intracranial malignancy. Due to the high rate of recurrence, the bad prognosis and inefficiency of existing therapies, there is the need for better understanding control mechanisms of invasion in GBM for the development of interventions that inhibit the progression of this cancer. ADAM family consists of a group of desintegrins and proteases zinc dependent that perform key roles in many processes contributing to physiological homeostasis and various diseases, such as cancer. ADAM23 appears to be preferentially expressed in the central nervous system and has a crucial physiological role in neuronal differentiation and brain development. In neoplastic tissues, it has been described silencing the expression of the ADAM23 gene in a wide range of tumors, such as breast, pancreatic, gastric tumors, head and neck, colorectal, lung and bone cancer. Although the relevance of the ADAM23 expression during embryonic and normal brain development and its inactivation during progression of different cancers, little is known about the molecular mechanisms regulated by this gene. In recent analysis, we found that astrocitomas with a more advanced grade (grade IV) showed higher frequency of ADAM23 downregulation than lower grades, suggesting that ADAM23 may be silenced during the progression of gliomas. Furthermore, we note first that ADAM23 inhibits cell invasion and presence of nuclear ²-catenin model neurosphere GBM. Knowing the importance of the Wnt pathway for progression of GBMs, added to our data supporting the hypothesis that ADAM23 acts as a Wnt pathway driver, this project appears in order to deepen this understanding and study the molecular mechanisms of control of invasive phenotype due to the silencing of ADAM23 in GBM, with main focus on the Wnt pathway. (AU)

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Scientific publications
(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)
JANDREY, ELISA HELENA FARIAS; BEZERRA, MARCELLE; INOUE, LILIAN TIEMI; FURNARI, FRANK B.; CAMARGO, ANAMARIA ARANHA; COSTA, ERICO TOSONI. A Key Pathway to Cancer Resilience: The Role of Autophagy in Glioblastomas. FRONTIERS IN ONCOLOGY, v. 11, . (16/07463-4, 16/06857-9)

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