A molecular study of desmosomes identifies a desmoglein isoform switch in head and neck squamous cell carcinoma.

Abstract

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 PKP1 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.

• Authors: Muy-Teck Teh, E Ken Parkinson, Johanna K Thurlow, Feng Liu, Farida Fortune, Hong Wan
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 40 Issue 1 Pg. 67-76 (Jan 2011) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 20923451 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Desmoglein 2
• Desmoglein 3
• Protein Isoforms
• RNA, Messenger

Topics

• Carcinoma, Squamous Cell (metabolism)
• Case-Control Studies
• Cell Transformation, Neoplastic (genetics, metabolism)
• Desmoglein 2 (genetics, metabolism)
• Desmoglein 3 (genetics, metabolism)
• Desmosomes (metabolism)
• Epidermal Cells
• Epidermis (metabolism)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Head and Neck Neoplasms (metabolism)
• Humans
• Keratinocytes (cytology, metabolism)
• Mouth Mucosa (cytology, metabolism)
• Oligonucleotide Array Sequence Analysis
• Precancerous Conditions (metabolism)
• Protein Isoforms
• RNA, Messenger (analysis)
• Reference Values