Wnt Signaling: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Abstract

Cellular maintenance and development are two fundamental mechanisms regulated by the canonical Wnt signaling pathway. Wnt/beta-catenin signaling pathway controls a myriad of cellular processes that are essential for normal cell functioning. Cell cycle progression, differentiation, fate determination, and migration are generally orchestrated by canonical Wnt signaling. Altered Wnt/beta-catenin signaling has been considered a promoting event for different types of cancers and the oncogenic potential of Wnt signaling have been discussed in many cancer types, including breast, colon, pancreatic as well as head and neck. Furthermore, Wnt signaling is critical for the maintenance and stemness of both the normal as well as cancer stem cells. This review sheds new light on Wnt signaling and explains how it can regulate normal physiological processes and curtail the development of cancer. It depicts the vital functions of Wnt signaling in the stem cell growth and differentiation by focusing on current druggable targets that have been ascribed by recent studies. Thus, Wnt signaling pathway retains a tremendous potential in eradicating head and neck squamous cell carcinoma.

Keywords: Wnt signaling; therapeutic target; head and neck squamous cell carcinoma.

Figure 1

Non-Canonical Wnt Signaling Pathway. In the absence of Wnt signaling (1) the β-catenin is targetd for degradation (2) (Phosphorylation) by the complex. The complex consists of tumor suppressor gen (APC), scaffold protein (Axin) and kinase ( CK 1, GSK)(3)

Figure 2

Canonical Wnt Signaling Pathway. In the presence of Wnt signaling, β-catenin degradation is inhibited. Wnt binds to Fzd and LRP receptors (1). Cytoplasmic protein DvL facilitates recruitment of the complex (formed by APC, Axin, CK1, GSK 3) at LRP level (2). Consequenlty β-catenin is free to translocate into the nucleus and interact with TCF/LET transcription factors to active target genes (3)