Junctional Adhesion Molecules in Cancer: A Paradigm for the Diverse Functions of Cell-Cell Interactions in Tumor Progression.

Abstract

Tight junction (TJ) proteins are essential for mediating interactions between adjacent cells and coordinating cellular and organ responses. Initial investigations into TJ proteins and junctional adhesion molecules (JAM) in cancer suggested a tumor-suppressive role where decreased expression led to increased metastasis. However, recent studies of the JAM family members JAM-A and JAM-C have expanded the roles of these proteins to include protumorigenic functions, including inhibition of apoptosis and promotion of proliferation, cancer stem cell biology, and epithelial-to-mesenchymal transition. JAM function by interacting with other proteins through three distinct molecular mechanisms: direct cell-cell interaction on adjacent cells, stabilization of adjacent cell surface receptors on the same cell, and interactions between JAM and cell surface receptors expressed on adjacent cells. Collectively, these diverse interactions contribute to both the pro- and antitumorigenic functions of JAM. In this review, we discuss these context-dependent functions of JAM in a variety of cancers and highlight key areas that remain poorly understood, including their potentially diverse intracellular signaling networks, their roles in the tumor microenvironment, and the consequences of posttranslational modifications on their function. These studies have implications in furthering our understanding of JAM in cancer and provide a paradigm for exploring additional roles of TJ proteins.

• Authors: Adam Lauko, Zhaomei Mu, David H Gutmann, Ulhas P Naik, Justin D Lathia
• Journal: Cancer research (Cancer Res) Vol. 80 Issue 22 Pg. 4878-4885 (11 15 2020) ISSN: 1538-7445 [Electronic] United States
• PMID: 32816855 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Junctional Adhesion Molecule A
• Junctional Adhesion Molecule C
• Junctional Adhesion Molecules
• Tumor Suppressor Proteins
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Apoptosis (physiology)
• Breast Neoplasms (etiology, pathology, physiopathology)
• Cell Adhesion (physiology)
• Cell Communication (physiology)
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Disease Progression
• Female
• Humans
• Junctional Adhesion Molecule A (chemistry, physiology)
• Junctional Adhesion Molecule C (physiology)
• Junctional Adhesion Molecules (chemistry, physiology)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasms (etiology, pathology, physiopathology)
• Receptor, ErbB-2 (metabolism)
• Structure-Activity Relationship
• Tight Junctions
• Tumor Microenvironment (immunology)
• Tumor Suppressor Proteins (physiology)