Wnt Signaling Pathways in Keratinocyte Carcinomas.

Christopher M R Lang,Chim Kei Chan,Anthony Veltri,Wen-Hui Lien

doi:10.3390/cancers11091216

Abstract

The skin functions as a barrier between the organism and the surrounding environment. Direct exposure to external stimuli and the accumulation of genetic mutations may lead to abnormal cell growth, irreversible tissue damage and potentially favor skin malignancy. Skin homeostasis is coordinated by an intricate signaling network, and its dysregulation has been implicated in the development of skin cancers. Wnt signaling is one such regulatory pathway orchestrating skin development, homeostasis, and stem cell activation. Aberrant regulation of Wnt signaling cascades not only gives rise to tumor initiation, progression and invasion, but also maintains cancer stem cells which contribute to tumor recurrence. In this review, we summarize recent studies highlighting functional evidence of Wnt-related oncology in keratinocyte carcinomas, as well as discussing preclinical and clinical approaches that target oncogenic Wnt signaling to treat cancers. Our review provides valuable insight into the significance of Wnt signaling for future interventions against keratinocyte carcinomas.

Highlights

The skin is the largest organ and functions as a protective barrier for the host to prevent fluid loss and regulate body temperature
One of the unique features for cutaneous SCC (cSCC) and HNSCC is their high degree elsewhere [116,117,118], we mainly focus on cSCC in this review
We emphasize the crucial roles of Wnt signaling in different aspects of keratinocyte carcinoma development, including their participation in tumor initiation, progression, invasion, and metastasis

Summary

Introduction

The skin is the largest organ and functions as a protective barrier for the host to prevent fluid loss and regulate body temperature. Several signaling pathways that have been shown to play vital roles in development of the skin epithelium are implicated in the progression of keratinocyte carcinoma, including hedgehog (Hh), transforming growth factor β (TGFβ), mitogen-activated protein kinase (MAPK/ERK) and. Canonical Wnt/β-catenin signaling is a major regulatory pathway that governs developmental processes as well as regulating maintenance and differentiation of adult stem cells (SCs) [8,9,10]. We summarize recent studies where the role of Wnt signaling in regulating tumor initiation and progression of keratinocyte carcinoma has been identified

Wnt Signaling Pathways

Wnt Signaling in Keratinocyte Carcinomas

Squamous

Potential Therapeutic Targeting of Wnt Signaling

Findings

Conclusions