Invasion and metastasis of oral cancer cells require methylation of E-cadherin and/or degradation of membranous beta-catenin.
The extent of lymph node metastasis is a major determinant in the prognosis of oral squamous cell carcinoma (OSCC). Abnormalities of cell adhesion molecules are known to play an important role in invasion and metastasis of cancer cells through the loss of cell-to-cell adhesion. In this study, we isolated highly invasive clones from an OSCC cell line established from a lymph node metastasis by using an in vitro invasion assay method and compared the abnormalities of cell adhesion molecule E-cadherin and beta-catenin in these cells. The isolated, highly invasive clones showed significant invasive capacity and reduction of E-cadherin and membranous beta-catenin protein in comparison with parent cells. We found that reduced expression of E-cadherin was due to methylation of its promoter region. In fact, most invasive and metastatic area of OSCCs showed reduced expression and methylation of E-cadherin. Moreover, we found that reduced expression of membranous beta-catenin was due to its protein degradation. Reduced expression of membranous beta-catenin was also found frequently in invasive and metastatic areas of OSCCs. In summary, invasion and metastasis of OSCC cells require methylation of E-cadherin and/or degradation of membranous beta-catenin. In addition, we suggest that the method of isolation of highly invasive clones may be useful for studies aimed at discovering novel genes involved in invasion and metastasis.
Department of Oral Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Yasusei
Y
Kudo
Shojiro
S
Kitajima
Ikuko
I
Ogawa
Masae
M
Hiraoka
Soodabeh
S
Sargolzaei
Mohammad Reza
MR
Keikhaee
Sunao
S
Sato
Mutsumi
M
Miyauchi
Takashi
T
Takata
D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D019175:DNA Methylation; D020868:Gene Silencing; D005887:Gingival Neoplasms / Q000235:genetics* / Q000473:pathology*; D006367:HeLa Cells; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D051176:beta Catenin