Abstract
Cadherin family includes lists of transmembrane glycoproteins which mediate calcium-dependent cell-cell adhesion. Cadherin-mediated adhesion regulates cell growth and differentiation throughout life. Through the establishment of the cadherin-catenin complex, cadherins provide normal cell-cell adhesion and maintain homeostatic tissue architecture. In the process of cell recognition and adhesion, cadherins act as vital participators. As results, the disruption of cadherin signaling has significant implications on tumor formation and progression. Altered cadherin expression plays a vital role in tumorigenesis, tumor progression, angiogenesis, and tumor immune response. Based on ongoing research into the role of cadherin signaling in malignant tumors, cadherins are now being considered as potential targets for cancer therapies. This review will demonstrate the mechanisms of cadherin involvement in tumor progression, and consider the clinical significance of cadherins as therapeutic targets.
Highlights
Cadherin was first described by Hyafil and Peyrieras in the 1980s as “Uvomorulin” in mouse and L-CAM in chicken [1, 2] and the mouse gene was later cloned [3]
Similar results have been found in several other cell lines that co-express N-cadherin and fibroblast growth factor receptor (FGFR)-1 [112], suggesting that the FGFR-Ncadherin signaling pathways might be general routes involved in metastasis
VE-cadherin could interact with vascular endothelial growth factor receptor (VEGFR)-2 (Figure 2C) and stimulate TGF-β signaling pathway to enhance cell proliferation [144]
Summary
Cadherin was first described by Hyafil and Peyrieras in the 1980s as “Uvomorulin” in mouse and L-CAM in chicken [1, 2] and the mouse gene was later cloned [3]. Cadherins act as modulators during organism growth. Tissue cohesion in organisms depends largely on cadherins. Radice et al [7] found that mice lacking N-cadherin (CDH2) developed heart defects and died in utero. Cadherins affect cell polarization, by differentiating between cell populations during development [8]; this function might has a relationship with intrinsic characteristics of the ectodomains of cadherins [9]. The research to date has focused on the relationship between cadherins and malignant tumors, and drugs targeting cadherins have been developed and tested in clinical trials. We intend to summarize the mechanisms whereby cadherins mediate tumor formation and progression, and to discuss their potential use in clinical treatment of cancer patients
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