Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

Author(s):Show less -

Coelho, Barbara Paranhos ^[1] ; de Lima Fernandes, Camila Felix ^[1] ; Boccacino, Jacqueline Marcia ^[1] ; da Silva Souza, Maria Clara ^[1] ; Melo-Escobar, Maria Isabel ^[1] ; Alves, Rodrigo Nunes ^[1] ; Prado, Mariana Brandao ^[1] ; Iglesia, Rebeca Piatniczka ^[1] ; Cangiano, Giovanni ^[1] ; Mazzaro, Giulia La Rocca ^[1] ; Lopes, Marilene Hohmuth ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Lab Neurobiol & Stem Cells, Sao Paulo - Brazil

• Document type: Review article
• Source: FRONTIERS IN ONCOLOGY; v. 10, NOV 12 2020.
• Web of Science Citations: 0

Abstract

Tumor cells can employ epithelial-mesenchymal transition (EMT) or autophagy in reaction to microenvironmental stress. Importantly, EMT and autophagy negatively regulate each other, are able to interconvert, and both have been shown to contribute to drug-resistance in glioblastoma (GBM). EMT has been considered one of the mechanisms that confer invasive properties to GBM cells. Autophagy, on the other hand, may show dual roles as either a GBM-promoter or GBM-suppressor, depending on microenvironmental cues. The Wingless (WNT) signaling pathway regulates a plethora of developmental and biological processes such as cellular proliferation, adhesion and motility. As such, GBM demonstrates deregulation of WNT signaling in favor of tumor initiation, proliferation and invasion. In EMT, WNT signaling promotes induction and stabilization of different EMT activators. WNT activity also represses autophagy, while nutrient deprivation induces beta-catenin degradation via autophagic machinery. Due to the importance of the WNT pathway to GBM, and the role of WNT signaling in EMT and autophagy, in this review we highlight the effects of the WNT signaling in the regulation of both processes in GBM, and discuss how the crosstalk between EMT and autophagy may ultimately affect tumor biology. (AU)

• FAPESP's process: 19/14552-1 - Analysis of differentially expressed genes in PRNPlow and PRNPhigh patient-derived glioblastoma stem cells
• Grantee: Giulia La Rocca Mazzaro
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/14952-0 - Characterization of intracellular signaling pathways modulated by the cellular prion protein on stemness maintenance in glioblastoma stem cells
• Grantee: Bárbara Paranhos Coelho
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 17/26158-0 - Prion protein as stem regulator in glioblastoma stem cells: its role in the formation and function of multiprotein signaling platforms
• Grantee: Mariana Brandão Prado
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/04687-4 - The role of neural stem cells extracellular vesicles in the modulation of phenotype of PRNP low and PRNP high glioblastoma stem cells
• Grantee: Rodrigo Nunes Alves
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/06971-4 - Evaluation of pluripotency and self-renewal of murine embryonic stem cells with differential expression of STI1
• Grantee: Maria Clara da Silva Souza
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/11097-1 - Modulation of the neural phenotype of glioblastoma stem cells by extracellular miRNA from NSCs
• Grantee: Maria Isabel Melo Escobar
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/12710-9 - Role of cellular prion protein in temozolomide resistance: emphasis on processes modulated by hypoxia
• Grantee: Rebeca Piatniczka Iglesia
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 20/07450-5 - Evaluation of transcript levels of PrPc downstream targets and intracellular signaling pathways in glioblastoma stem cells
• Grantee: Jacqueline Marcia Boccacino
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/15557-4 - Prion protein and its partners: emerging targets for glioblastoma stem cell based-therapy
• Grantee: Marilene Hohmuth Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 19/14741-9 - Study of the role of STI1 and assotiated factors in the proteostasis network and pluripotency regulation
• Grantee: Camila Felix de Lima Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)