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Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics

Published on: March 26, 2018

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

Adam Lauko^1,2,3, Zhaomei Mu⁴, David H Gutmann⁵

¹Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Cancer Research

|August 21, 2020

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.

Insights

Junctional adhesion molecules (JAMs) initially thought to suppress tumors now show protumorigenic roles in cancer. Their complex interactions highlight context-dependent functions needing further research.

Area of Science:

Oncology
Cell Biology
Molecular Biology

Background:

Tight junction (TJ) proteins regulate cell interactions and responses.
Junctional adhesion molecules (JAMs) were initially linked to tumor suppression, with reduced expression correlating with metastasis.
Recent research reveals JAM-A and JAM-C possess protumorigenic functions, promoting proliferation and inhibiting apoptosis.

Purpose of the Study:

To review the context-dependent roles of JAMs in various cancers.
To highlight poorly understood aspects of JAM function, including signaling, tumor microenvironment interactions, and posttranslational modifications.

Main Methods:

Literature review of studies on JAM proteins in cancer.
Analysis of molecular mechanisms underlying JAM interactions.
Discussion of emerging research on JAMs' roles in cancer progression.

Main Results:

JAMs exhibit dual roles, acting as both tumor suppressors and promoters depending on the cancer context.
JAMs interact with other proteins via three distinct mechanisms, influencing cell adhesion and signaling.
Protumorigenic functions include promoting proliferation, cancer stem cell biology, and epithelial-to-mesenchymal transition.

Conclusions:

JAMs have complex, context-dependent roles in cancer, with both pro- and anti-tumorigenic functions.
Further research is needed to elucidate JAMs' intracellular signaling, tumor microenvironment roles, and posttranslational modification effects.
Understanding JAMs offers a paradigm for exploring other TJ proteins in cancer.

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