Intraepithelial p63-dependent expression of distinct components of cell adhesion complexes in normal esophageal mucosa and squamous cell carcinoma.
TP63 gene is a member of TP53 tumor suppressor gene family that encodes several protein isoforms involved in the process of epithelial stratification and in epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper-expression of DeltaNp63 as the major p63 isoform. To better understand the contribution of this high expression to tumorigenesis, we have analyzed the impact of intraepithelial p63 expression on the expression of cell adhesion complexes in normal esophagus and in ESCC cell lines. Cells expressing p63 showed an adhesion pattern characterized by lack of tight junctions and presence of adherens junctions. Cell differentiation was accompanied by a decrease in p63 and by a shift to adhesion patterns involving tight junctions. Silencing of p63 mRNA in ESCC cell lines resulted in a similar shift, characterized by increased expression of component of tight junctions, decreased cell-to-cell communication and downregulation of cell proliferation. These results indicate that DeltaNp63 may contribute to esophageal squamous carcinogenesis by maintaining cell adhesion patterns compatible with cell proliferation.
Thépot
Amélie
A
Molecular Carcinogenesis Group and Epigenetics Group, IARC, Lyon, France.
Hautefeuille
Agnès
A
Cros
Marie-Pierre
MP
Abedi-Ardekani
Behnoush
B
Pétré
Aurélia
A
Damour
Odile
O
Krutovskikh
Vladimir
V
Hainaut
Pierre
P
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53