Introduction of ID2 Enhances Invasiveness in ID2-null Oral Squamous Cell Carcinoma Cells via the SNAIL Axis.
OBJECTIVE
Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells.


METHODS
We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP).


RESULTS
ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1).


CONCLUSIONS
ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2-SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC.
Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Y U
YU
Kamata
Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan tomoki@dent.kyushu-u.ac.jp.
Tomoki
T
Sumida
Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Yosuke
Y
Kobayashi
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
Akiko
A
Ishikawa
Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Wataru
W
Kumamaru
Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Yoshihide
Y
Mori
D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000235:genetics*; D014746:Vimentin / Q000096:biosynthesis
D015820:Cadherins; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014746:Vimentin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
Inhibitor of differentiation; SNAIL; epithelial–mesenchymal transition; invasion; matrix metalloproteinase