Tumor-Derived Exosomes Mediate the Instability of Cadherins and Promote Tumor Progression.

Bowen Wang,Feng Guan,Zengqi Tan

doi:10.3390/ijms20153652

Bowen Wang, Feng Guan + Show 1 more

Open Access

https://doi.org/10.3390/ijms20153652

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Abstract

Cadherins, including E-cadherin, N-cadherin, VE-cadherin, etc., are important adhesion molecules mediating intercellular junctions. The abnormal expression of cadherins is often associated with tumor development and progression. Epithelial–mesenchymal transition (EMT) is the most important step in the metastasis cascade and is accompanied by altered expression of cadherins. Recent studies reveal that as a cargo for intercellular communication, exosomes—one type of extracellular vesicles that can be secreted by tumor cells—are involved in a variety of physiological and pathological processes, especially in tumor metastasis. Tumor-derived exosomes play a crucial role in mediating the cadherin instability in recipient cells by transferring bioactive molecules (oncogenic microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), EMT-related proteins, and others), modulating their local and distant microenvironment, and facilitating cancer metastasis. In turn, aberrant expression of cadherins in carcinoma cells can also affect the biogenesis and release of exosomes. Therefore, we summarize the current research on the crosstalk between tumor-derived exosomes and aberrant cadherin signals to reveal the unique role of exosomes in cancer progression.

Highlights

Introduction of ExosomesExtracellular vesicles (EVs) are nanoscale vesicles secreted by cells, including apoptotic bodies, exosomes, and microvesicles
Exosomes are encapsulated by proteins and lipids, and contain functional proteins and genetic material, such as mRNAs, microRNAs, and long non-coding RNAs
Cytoskeleton-associated proteins-enriched exosomes from metastatic colon cancer cells affected the integrity of endothelial cells by inducing a clear cytosolic delocalization of the adherens junction proteins including β-catenin, p120-catenin, and VE-cadherin, without changes of VE-cadherin expression at both mRNA and protein levels, through RhoA/Rock signaling in recipient cells. p53 deficient mouse bone marrow mesenchymal stem cells (MSCs) exosomes enriched ubiquitin protein ligase E3 component N-recognin 2 (UBR2) resulted in the increased proliferation and migration of p53+/+ mBMMSC and murine foregastric carcinoma (MFC) by activating Wnt/β-catenin signaling with changed Epithelial–mesenchymal transition (EMT) marker expression including E-/N-cadherin [113]

Summary

Introduction of Exosomes

Extracellular vesicles (EVs) are nanoscale vesicles secreted by cells, including apoptotic bodies, exosomes, and microvesicles. MVEs have two destinies: one is to enter lysosome and be degraded; the other is to fuse with the plasma membrane and release intraluminal vesicles (ILVs), i.e., exosomes, into extracellular environment [3,4] (Figure 1). RNAs (including microRNAs and allows lncRNAs), proteins, exosomes to the extracellular milieu. TGN: trans-Golgi network; ICAM-1: intercellular cell adhesion molecule-1; and MHC: microRNAs and lncRNAs), proteins, and lipids. Exosomes are encapsulated by proteins and lipids, and contain functional proteins and genetic material, such as mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). Patients with different types of cancer release exosomes which contain different signatures of miRNAs into the circulation, which can be measured as diagnostic biomarkers [19]. We summarize recent studies on the instability of cadherins and tumor progression mediated by tumor-derived exosomes

Key Role of Cadherins in EMT

Exosomal miRNAs and Cadherins

Exosomal Proteins and Cadherins

Conclusions

A schematic

Methods