Clinical significance of altered expression of β-catenin and E-cadherin in oral dysplasia and cancer: potential link with ALCAM expression

• Published in: PloS one 2013-06, Vol.8 (6), p.e67361-e67361
• Main Authors: Kaur, Jatinder, Sawhney, Meenakshi, DattaGupta, Siddhartha, Shukla, Nootan Kumar, Srivastava, Anurag, Walfish, Paul G, Ralhan, Ranju
• Format: Article
• Language: English
• Subjects: Accumulation; Adhesion; Adult; Aged; Aggressive behavior; Alterations; Antigens, CD - genetics; Antigens, CD - metabolism; beta Catenin - genetics; beta Catenin - metabolism; Biology; Cadherins - genetics; Cadherins - metabolism; Cancer; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; Cell Line, Tumor; Clinical significance; Confocal microscopy; Correlation; Disease Progression; Dysplasia; E-cadherin; Female; Fetal Proteins - genetics; Fetal Proteins - metabolism; Gene Expression; Gene Knockdown Techniques; Hospitals; Humans; Hyperplasia; Immunohistochemistry; Kaplan-Meier Estimate; Kinases; Laboratories; Lesions; Male; Medical prognosis; Medicine; Metastases; Metastasis; Microscopy; Middle Aged; Mouth Neoplasms - metabolism; Mouth Neoplasms - mortality; Multivariate Analysis; Neck; Oncology; Oral cancer; Oral squamous cell carcinoma; Otolaryngology; Pathology; Polymerase chain reaction; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Prognosis; Regression analysis; RNA, Small Interfering - genetics; siRNA; Squamous cell carcinoma; Surgery; Tissues; Transcription; Tumorigenesis; Tumors; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0067361

Perturbations in cell adhesion molecules are linked to alterations in cadherin-catenin complexes and likely play major roles in invasion and metastasis; their impact on early precancerous stages remains yet unknown. We showed ALCAM overexpression in early oral lesions and its cytoplasmic accumulation in oral squamous cell carcinoma (OSCC) to be a predictor of disease progression and poor prognosis. This study tested the hypothesis that alterations in E-cadherin and β -catenin expressions are early events in oral tumorigenesis, associated with disease prognosis, and correlate with perturbations in ALCAM expression. Expressions of E-cadherin and β-catenin were analyzed in the same cohort of 105 OSCCs, 76 oral lesions and 30 normal oral tissues by immunohistochemistry and correlated with clinicopathological parameters and prognosis. The effect of siRNA mediated ALCAM knockdown on E-cadherin and β -catenin was determined using western blot, confocal microscopy and RT-PCR analysis in oral cancer cells. Significant loss of membranous E-cadherin and β-catenin expression was observed from normal, hyperplasia, dysplasia to OSCCs (p(trend)