TEAD1 mediates the oncogenic activities of Hippo-YAP1 signaling in osteosarcoma

Journal Article · Sat Jun 24 04:00:00 EDT 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.05.032· OSTI ID:22719005

Chai, Jiwei; Xu, Shijie ^[1]; Guo, Fengbo ^[2]

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1. The Second Department of Trauma Surgery, Linyi People's Hospital, Linyi 276000 (China)
2. Chinese Medicine Department of Orthopedics, Linyi People's Hospital, Linyi 276000 (China)

Hippo signaling pathway is an evolutionarily conserved developmental network that governs the downstream transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs that responsible for cell proliferation, apoptosis, and stem cell self renewal. Emerging evidence has shown the tumor suppressor properties of Hippo signaling. However, limited knowledge is available concerning the downstream transcription factors of Hippo pathway in osteosarcoma (OS). In this study, we demonstrated that TEAD1 was the major transcription factor of Hippo signaling pathway in OS. Genetic silencing of TEAD1 suppressed multiple malignant phenotypes of OS cells including cell proliferation, apoptosis resistance, and invasive potential. Mechanistically, we showed that TEAD1 largely exerted its transcriptional control of its functional targets, PTGS2 and CYR61. Collectively, this work identifies the YAP1/TEAD1 complex as the representative dysregulated profile of Hippo signaling in OS and provides proof-of-principle that targeting TEAD1 may be a therapeutic strategy of osteosarcoma. - Highlights: •TEAD1 is the major downstream transcriptional factor of Hippo-YAP1 signaling in OS. • Knockdown of TEAD1 inhibits cell proliferation, invasion and promotes cell apoptosis in OS. • PTGS2 and CYR61 are required for the oncogenic roles of TEAD1 in OS.

• OSTI ID: 22719005
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 488; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
COMPLEXES
GENETICS
OSTEOSARCOMAS
PHENOTYPE
STEM CELLS
TRANSCRIPTION
TRANSCRIPTION FACTORS