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A molecular study of desmosomes identifies a desmoglein isoform switch in head and neck squamous cell carcinoma
Author(s) -
Teh MuyTeck,
Ken Parkinson E.,
Thurlow Johanna K.,
Liu Feng,
Fortune Farida,
Wan Hong
Publication year - 2011
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2010.00951.x
Subject(s) - desmoglein , biology , desmoglein 3 , desmosome , keratin , intermediate filament , pathology , cancer research , oral mucosa , malignancy , head and neck squamous cell carcinoma , gene knockdown , cancer , cadherin , cell culture , head and neck cancer , cell , medicine , immunology , anatomy , genetics , cytoskeleton , autoimmune disease , antibody
J Oral Pathol Med (2011) 40 : 67–76 Desmosomes, the intercellular junctions that confer strong adhesion between epithelial cells, are frequently altered in malignancy. However, a comprehensive analysis of these structures has not been carried out in oral neoplasia. Oral squamous cell carcinomas (SCCs) and pre‐malignant dysplasia can be sub‐classified according to their in vitro replicative lifespan, where the immortal dysplasia (ID) and carcinoma (IC) subsets have p16 ink4a and p53 dysfunction, telomerase deregulation and genetic instability and the mortal subset (MD and MC) do not. We found that the desmosomal proteins exhibit a distinct expression pattern in oral mucosa when compared with epidermis in vivo . Microarray data from a large panel of lines revealed that the transcript levels of DSG3 , DSC2/3 , DP , PG and PKP 1 were reduced in ID and IC. Interestingly, DSG2 was up‐regulated in MC. Reduction of DSG3 and up‐regulation of DSG2 were found in two independent microarray datasets. Significantly, we demonstrated that reduction of DSG3 and up‐regulation of DSG2 was reversible in vitro by using RNAi‐mediated knockdown of DSG2 in IC cells. The remaining desmosomal proteins were largely disrupted or internalized and associated with retraction of keratin intermediate filaments in oral SCC lines. These findings suggest dysfunction and loss of desmosomal components are common events in the immortal class of oral SCC and that these events may precede overt malignancy.