TMIGD1 - TMIGD1 Emerging functions of a tumor supressor and adhesion receptor - review

Sep 24, 2026

Review article analyzing TMIGD1, a transmembrane immunoglobulin superfamily member, focusing on how its two Ig-like domains and PDZ-binding motif enable adhesion-related signaling. The text explains TMIGD1’s molecular features and extracellular versus cytoplasmic interactions with scaffolding proteins, then connects these mechanisms to pleiotropic regulation of epithelial cell behavior. It further summarizes evidence for TMIGD1’s downregulation and tumor-suppressive relevance in colorectal and renal cancers, including impacts on proliferation, migration, mitochondria, and brush border assembly.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

INTRODUCTION

TMIGD1 molecular characteristics

Structure and PDZ-binding motif

Interactions with cytoplasmic scaffolding proteins

Regulation of TMIGD1 expression in cancer

Downregulation in colorectal and renal cancers

Oncogene [www.nature.com/onc](www.nature.com/onc) REVIEW ARTICLE OPEN TMIGD1: Emerging functions of a tumor supressor and adhesion receptor Eva-Maria Thüring 1, Christian Hartmann1, Ysabel A. Schwietzer1 and Klaus Ebnet 1 ✉ © The Author(s) 2023 | | | | | --- | --- | --- | | | The development of multicellular organisms depends on cell adhesion molecules (CAMs) that connect cells to build tissues. The immunoglobulin superfamily (IgSF) constitutes one of the largest families of CAMs. Members of this family regulate such diverse processes like synapse formation, spermatogenesis, leukocyte-endothelial interactions, or epithelial cell-cell adhesion. Through their extracellular domains, they undergo homophilic and heterophilic interactions in cis and trans. Their cytoplasmic domains frequently bind scaffolding proteins to assemble signaling complexes. Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is a IgSF member with two Ig-like domains and a short cytoplasmic tail that contains a PDZ domain-binding motif. Recent observations indicate that TMIGD1 has pleiotropic functions in epithelial cells and has a critical role in suppressing malignant cell behavior. Here, we review the molecular characteristics of TMIGD1, its interaction with cytoplasmic scaffolding proteins, the | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | regulation of its expression, and its downregulation in colorectal and renal cancers. | | | | | Oncogene (2023) 42:1777–1785; [https://doi.org/10.1038/s41388-023-02696-5](https://doi.org/10.1038/s41388-023-02696-5) | | | | | | INTRODUCTION Epithelia consist of sheets of cells in which cells are connected by intercelluar junctions. Individual cells are highly polarized with an apical membrane domain facing the cell-free outside of an organ, a lateral domain contacting the adjacent cell, and a basal membrane domain that is attached to the underlying extracellular matrix [1] . This organization is commonly referred to as apico-basal polarity [2] . A loss of apico-basal polarity does not only impair the functioning of the individual cell but is frequently associated with malignant growth [1] . A loss of apicobasal polarity is also frequently associated with a loss of cell-cell adhesion and with a transition from an epithelial phenotype to amesenchymal phenotype, thus predisposing cells to dissemination and metastasis formation [3–5] . The intercellular adhesion of epithelial cells is mediated by different cell adhesion receptors, in particular cell adhesion receptors of the cadherin and of the immunoglobulin (Ig) superfamilies (SF) . Many adhesion receptors are incorporated into structural networks at speciﬁc membrane domains like adherens junctions (AJs), tight junctions (TJs) or desmosomes [6] . A common feature of these adhesive networks is their association with the actin cytoskeleton or the intermediate ﬁlament system through direct or indirect interacions of adhesion receptors with cytoplasmic scaffolding proteins [7] . Another commonality of adhesive networks is an extensive cross-talk with other adhesive structures, both at sites of cell-cell adhesion and at sites of cell-matrix adhesion [8–11] . This enables cells to integrate signals originating from different adhesive sites, and to transform these signals into coordinated cell behavior, as it is required during collective cell migration or during morphogenesis [12, 13] . Thus, cell-cell adhesion receptorbased structures not only provide mechanical links between individual cells but represent critical signaling networks that orchestrate cell behavior at the tissue scale. Given the critical role of cell-cell adhesion receptors in maintaining tissue integrity both by their adhesive function and by their signaling function, it is not surprising that the expression levels of cell-cell adhesion receptors are frequently altered in malignancies. For example, during epithel

FAQs

What is TMIGD1 and what family does it belong to?

TMIGD1 is a transmembrane and immunoglobulin domain-containing protein 1 and a member of the immunoglobulin superfamily (IgSF). It contains two Ig-like domains and a short cytoplasmic tail with a PDZ domain-binding motif.

How does TMIGD1 potentially influence cell behavior in epithelial cells?

The review links TMIGD1 to multiple pleiotropic functions in epithelial cells, including regulation of cell proliferation and migration, mitochondrial activity, and brush border assembly. These effects are associated with its capacity to assemble signaling complexes via cytoplasmic interactions.

Why is TMIGD1 considered relevant to cancer?

TMIGD1 shows progressive downregulation during colorectal cancer development. The article summarizes evidence that TMIGD1 suppresses malignant cell behavior and highlights reduced expression in colorectal and renal cancers.

Sep 24, 2026

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