Abstract

Alterations in the extracellular matrix (ECM) likely facilitate the first steps of cancer cell metastasis and supports tumor progression. Recent data has demonstrated that alterations in collagen XVII (BP180), a transmembrane protein and structural component of the ECM, can have profound effects on cancer invasiveness. Collagen XVII is a homotrimer of three α1 (XVII) chains. Its intracellular domain contains binding sites for plectin, integrin β4, and BP230, while the extracellular domain facilitates interactions between the cell and the ECM. Collagen XVII and its shed ectodomain have been implicated in cell motility and adhesion and are believed to promote tumor development and invasion. A strong association of collagen XVII ectodomain shedding and tumor invasiveness occurs in squamous cell carcinoma (SCC). Aberrant expression of collagen XVII has been reported in many epithelial cancers, ranging from squamous cell carcinoma to colon, pancreatic, mammary, and ovarian carcinoma. Thus, in this review, we focus on collagen XVII's role in neoplasia and tumorigenesis. Lastly, we discuss the importance of targeting collagen XVII and its ectodomain shedding as a novel strategy to curb tumor growth and reduce metastatic potential.

Highlights

  • Cancer is a leading cause of death in developed countries [1]

  • XVII ectodomain shedding in squamous cell carcinoma, it appears that collagen XVII may play a important role in epithelial cancer growth and invasiveness

  • The intracellular domain (ICD) of collagen XVII consists of 466 amino acids while the transmembrane domain (TD) and extracellular domain (ECD) are 23 and 1,008aa, respectively [21]

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Summary

Frontiers in Oncology

Alterations in the extracellular matrix (ECM) likely facilitate the first steps of cancer cell metastasis and supports tumor progression. Recent data has demonstrated that alterations in collagen XVII (BP180), a transmembrane protein and structural component of the ECM, can have profound effects on cancer invasiveness. Collagen XVII and its shed ectodomain have been implicated in cell motility and adhesion and are believed to promote tumor development and invasion. A strong association of collagen XVII ectodomain shedding and tumor invasiveness occurs in squamous cell carcinoma (SCC). Aberrant expression of collagen XVII has been reported in many epithelial cancers, ranging from squamous cell carcinoma to colon, pancreatic, mammary, and ovarian carcinoma. We discuss the importance of targeting collagen XVII and its ectodomain shedding as a novel strategy to curb tumor growth and reduce metastatic potential

INTRODUCTION
Collagen XVII and Cancer
Ectodomain Shedding
FUNCTIONAL ROLES OF COLLAGEN XVII
The Role of Collagen XVII in Cell Differentiation
The Role of Collagen XVII in Cell Migration
The Role of Collagen XVII in Skin Inflammation
INVOLVEMENT OF COLLAGEN XVII IN CANCER DEVELOPMENT
Collagen XVII as It Pertains to Skin Cancer
Collagen XVII as It Pertains to Other Cancers
Cervical cancer
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