WNT Pathway in Laryngeal Squamous Cell Carcinoma and Nasopharyngeal Carcinoma

摘要

WNT proteins are a large family of secreted glycoproteinsactivating the WNT-pathway. WNT binding to Frizzled(Fz) results in the activation of Dishevelled (Dsh),which inhibits the activity of GSK3-b, resulting in dephosphorylationand stabilization of b-catenin, enablingit to accumulate within the nucleus, where it interacts withmembers of the T-cell factor/lymphocyte enhancer factor(TCF/LEF) family of trans-cription factors to stimulatethe expression of target genes. In summary, the canonicalpathway translates a WNT signal into the transient transcriptionof a TCF/LEF target gene programme. Nuclearb-catenin then interacts with various transcription factorsto cause cellular proliferation and differentiation. Thereare several WNT-antagonists that may be classified in twotypes: a) those that interfere with WNT activity by bindingto low-density lipoprotein receptor-related proteins(LRP-5 or LRP-6), including Sclerostin and Dickkopf(DKK) proteins, and b) those that interact directly withWNT proteins, including WIF-1. Although the role of theWNT pathway in nasopharyngeal carcinoma (NPC) hasnot been fully explored, there is abundant evidence thataberrant WNT signalling is involved in its development 1 2.Very little data is available on this pathway in laryngealsquamous cell carcinoma (LSCC) 3-5. Cytoplasmic b-cateninplays a major role in the normal cell by binding tothe intracellular domain of E-cadherin to maintain cellcelladhesion. The expression of E-cadherin has beenfound to be down-regulated in many cancers includingnasopharyngeal carcinoma 2 3. It has been suggested thatE-cadherin down-regulation may play a role in tumourprogression and metastasis. Strong b-catenin expressionis significantly associated with invasion and metastasis ofcarcinomas of the head and neck, oesophagus, stomach,colon, liver, lung, breast, female genitalia, prostate, bladderand pancreas, as well as melanoma. Recently, severalstudies have pointed to the considerable involvement ofb-catenin, not only in malignant transformation