DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis

Abstract

To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer (HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription-polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P ¼ 0.009), N stage (P ¼ 0.047), overall stage (P ¼ 0.011), tumor depth (P ¼ 0.009) and extracapsular spread in lymph nodes (P ¼ 0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57-21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30-48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.

Desmoglein 3 is overexpressed in inverted papilloma and squamous cell carcinoma of sinonasal cavity

“…In these studies, DSG3 was overexpressed in poor outcome patients of oral squamous cell carcinoma and was implied to associate with cancer-invasive and metastatic potential. 5,6 The conflicting data produced by us and other investigators might be explained by the following mechanisms. First, little is known about the ways in which desmosomal cadherins interact with each other to generate adhesion.…”

“…First, little is known about the ways in which desmosomal cadherins interact with each other to generate adhesion. Therefore, the quenching effect was proposed by Chen et al 5 The overexpression of DSG3 will result in some associated desmosome proteins binding, and thus disrupt the stability or kinetics of the desmosome structure. It will further facilitate tumor formation and cell migration.…”

“…Among the desmosomes, desmoglein 3 (DSG3) was found to be overexpressed in head and neck SCC, but not in other nonsquamous malignancy or normal mucosa tissues. 5,6 However, little is known about Editor the transformation mechanism of IP and the role of DSG3 in these processes. To provide some basic insight into how to manage IP, we examined the levels of DSG3 in both sinonasal IP, IP with SCC, and normal sinus mucosa by using immunohistochemistry and/or real-time polymerase chain reaction (PCR).…”

Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention

“…Cloning of Small Interfering RNA Plasmid The pTOPO-U6 vector was used to construct a Grp78-small interfering RNA (siRNA) and Grp78-scramble plasmid as described previously (22,23) in which a 22-nucleotide sense and antisense hairpin oligonucleotide was generated complementary to Grp78 mRNA. This hairpin oligonucleotide included two restriction enzyme cleavage sites corresponding to the blunt and overhanging end matching EcoRV-and BbsI-digested pTOPO-U6.…”

Broken hearts, woolly hair, and tattered skin: when desmosomal adhesion goes awry

“…Along the same lines, DSC2 and DSC3 expression is downregulated in colorectal and breast cancer, respectively [44,45]; whereas DSG3 is overexpressed in squamous cell carcinoma and head and neck cancer [43,46]. In general, whether desmosomes are involved in cancer and metastasis is very poorly understood [47].…”