title: The Hippo transducer TAZ promotes cell proliferation and tumor formation of glioblastoma cells through EGFR pathway.
abstract: TAZ, a WW-domain-containing transcriptional co-activator, is important for development of various tissues in mammals. Recently, TAZ has been found to be overexpressed in some types of human cancers. However, the role of TAZ in glioblastoma remains unclear. In this study, we found that TAZ was overexpressed in prognostically poor glioblastoma patients. Through knocking down or overexpressing TAZ in U87 and LN229 cells, the expression level of TAZ was found to be positively related to cell proliferation in vitro and tumor formation in vivo. Further investigation indicated that TAZ could significantly promote the acceleration of cell cycle. Moreover, the western blot for p-EGFR, p-AKT, p-ERK1/2, p21, cyclin E and CDK2 proteins, target genes of the EGFR pathway, indicated that TAZ significantly activated EGFR/AKT/ERK signaling. Additionally, the blockage of EGFR pathway resulted in a significantly inhibition of cell proliferation induced by TAZ. Taken together, these results demonstrate that TAZ can promote proliferation and tumor formation in glioblastoma cells by potentiating the EGFR/AKT/ERK pathway, and provide the evidence for promising target for the treatment of glioblastoma.
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Neurosurgery, Second Artillery General Hospital, Chinese People's Liberation Army, Beijing 100088, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Chongqing Reproductive and Genentics Institute, Chongqing Obstetrics and Gynecology Hospital, Chongqing 400013, China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014183:Transplantation, Heterologous
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: EGFR; TAZ; cell cycle; cell proliferation; glioblastoma