RRC ID 52139
Author Takeuchi S, Kasamatsu A, Yamatoji M, Nakashima D, Endo-Sakamoto Y, Koide N, Takahara T, Shimizu T, Iyoda M, Ogawara K, Shiiba M, Tanzawa H, Uzawa K.
Title TEAD4-YAP interaction regulates tumoral growth by controlling cell-cycle arrest at the G1 phase.
Journal Biochem. Biophys. Res. Commun.
Abstract TEA domain transcription factor 4 (TEAD4), which has critical functions in the process of embryonic development, is expressed in various cancers. However, the important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain unclear. Here we investigated the TEAD4 expression level and the functional mechanism in OSCC using quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4 knockdown model was used to evaluate cellular proliferation, cell-cycle analysis, and the interaction between TEAD4 and Yes-associated protein (YAP) which was reported to be a transcription coactivator of cellular proliferation. In the current study, we found that TEAD4 expression increased significantly in vitro and in vivo and correlated with tumoral size in OSCC patients. TEAD4 knockdown OSCC cells showed decreased cellular proliferation resulting from cell-cycle arrest in the G1 phase by down-regulation of cyclins, cyclin-dependent kinases (CDKs), and up-regulation of CDK inhibitors. We also found that the TEAD4-YAP complex in the nuclei may be related closely to transcriptions of G1 arrest-related genes. Taken together, we concluded that TEAD4 might play an important role in tumoral growth and have potential to be a therapeutic target in OSCCs.
Volume 486(2)
Pages 385-390
Published 2017-4-29
DOI 10.1016/j.bbrc.2017.03.050
PII S0006-291X(17)30504-1
PMID 28315328
MeSH Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Aged Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Carcinoma, Squamous Cell / surgery Cell Line, Tumor Cell Nucleus / genetics Cell Nucleus / metabolism Cell Proliferation Cyclin D1 / genetics Cyclin D1 / metabolism Cyclin E / genetics Cyclin E / metabolism Cyclin-Dependent Kinase 2 / genetics Cyclin-Dependent Kinase 2 / metabolism Cyclin-Dependent Kinase 4 / genetics Cyclin-Dependent Kinase 4 / metabolism Cyclin-Dependent Kinase 6 / genetics Cyclin-Dependent Kinase 6 / metabolism Cyclin-Dependent Kinase Inhibitor p21 / genetics Cyclin-Dependent Kinase Inhibitor p21 / metabolism Cyclin-Dependent Kinase Inhibitor p27 / genetics Cyclin-Dependent Kinase Inhibitor p27 / metabolism DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Female G1 Phase Cell Cycle Checkpoints* Gene Expression Regulation, Neoplastic* Humans Male Middle Aged Mouth Neoplasms / genetics* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology Mouth Neoplasms / surgery Muscle Proteins / antagonists & inhibitors Muscle Proteins / genetics* Muscle Proteins / metabolism Phosphoproteins / genetics* Phosphoproteins / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Signal Transduction Transcription Factors / antagonists & inhibitors Transcription Factors / genetics* Transcription Factors / metabolism Transcription, Genetic
IF 2.559
Resource
Human and Animal Cells Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Sa3(RCB0980) SAS(RCB1974)