The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance

Autor: Matthew R. Sarkisian, Brent A. Reynolds, Marius D. Kupper, Kelly G. Devers, Daniel J. Silver, Thomas Brabletz, Bugra Tugertimur, Oleg Suslov, Antony T. Yachnis, Dorit Siebzehnrubl, Simone Brabletz, Michael P. Kladde, Dennis A. Steindler, Daniel Neal, Florian A. Siebzehnrubl, Loic P. Deleyrolle, Nancy H. Nabilsi
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Mice
SCID
Mice
0302 clinical medicine
glioma
Receptors
Immunologic
DNA Modification Methylases
Research Articles
Zinc finger
0303 health sciences
Brain Neoplasms
EMT
3. Good health
Dacarbazine
Gene Expression Regulation
Neoplastic
Treatment Outcome
030220 oncology & carcinogenesis
Molecular Medicine
Female
medicine.drug
cancer stem cell
Cell Survival
brain
Kruppel-Like Transcription Factors
Antineoplastic Agents
Nerve Tissue Proteins
Biology
OLIG2
03 medical and health sciences
Proto-Oncogene Proteins c-myb
ROBO1
Cancer stem cell
Glioma
Cell Line
Tumor
medicine
Temozolomide
Animals
Humans
Neoplasm Invasiveness
xenograft
Transcription factor
neoplasms
030304 developmental biology
Homeodomain Proteins
Tumor Suppressor Proteins
Cancer
Zinc Finger E-box-Binding Homeobox 1
medicine.disease
DNA Repair Enzymes
Drug Resistance
Neoplasm
Cancer research
Glioblastoma
Neoplasm Transplantation
Transcription Factors
Zdroj: EMBO Molecular Medicine
ISSN: 1757-4684
1757-4676
Popis: Glioblastoma remains one of the most lethal types of cancer, and is the most common brain tumour in adults. In particular, tumour recurrence after surgical resection and radiation invariably occurs regardless of aggressive chemotherapy. Here, we provide evidence that the transcription factor ZEB1 (zinc finger E-box binding homeobox 1) exerts simultaneous influence over invasion, chemoresistance and tumourigenesis in glioblastoma. ZEB1 is preferentially expressed in invasive glioblastoma cells, where the ZEB1-miR-200 feedback loop interconnects these processes through the downstream effectors ROBO1, c-MYB and MGMT. Moreover, ZEB1 expression in glioblastoma patients is predictive of shorter survival and poor Temozolomide response. Our findings indicate that this regulator of epithelial-mesenchymal transition orchestrates key features of cancer stem cells in malignant glioma and identify ROBO1, OLIG2, CD133 and MGMT as novel targets of the ZEB1 pathway. Thus, ZEB1 is an important candidate molecule for glioblastoma recurrence, a marker of invasive tumour cells and a potential therapeutic target, along with its downstream effectors. Glioblastoma have a poor prognosis, mainly due to infiltrating and therapy resistant cells leading to cancer recurrence. Here, tumor formation, invasion and resistance are not independent but intertwined processes regulated by the EMT activator ZEB1.
Databáze: OpenAIRE
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