TEAD4-YAP interaction regulates tumoral growth by controlling cell-cycle arrest at the G1 phase.
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.
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shin
S
Takeuchi
Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan. Electronic address: kasamatsua@faculty.chiba-u.jp.
Atsushi
A
Kasamatsu
Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
Masanobu
M
Yamatoji
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
Dai
D
Nakashima
Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
Yosuke
Y
Endo-Sakamoto
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nao
N
Koide
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
Toshikazu
T
Takahara
Division of Oral Surgery, Kashima Rosai Hospital, Ibaraki, Japan.
Toshihiro
T
Shimizu
Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan.
Manabu
M
Iyoda
Division of Oral Surgery and Oral Implant Center, Funabashi Central Hospital, Chiba, Japan.
Katsunori
K
Ogawara
Department of Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Masashi
M
Shiiba
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
Hideki
H
Tanzawa
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan. Electronic address: uzawak@faculty.chiba-u.jp.
Katsuhiro
K
Uzawa
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; C530104:CCND1 protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495894:CDK2 protein, human; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6
Human oral squamous cell carcinoma; TEA domain transcription factor 4; Yes-associated protein (YAP)