Epithelial Membrane Proteins in Cancer Biology

Epithelial membrane proteins (EMPs) constitute a small subfamily of tetraspan proteins characterised by four transmembrane helices. The principal members—EMP1, EMP2 and EMP3—are encoded within the growth arrest‐specific 3 (GAS3)/peripheral myelin protein 22 (PMP22) gene family and contribute to fundamental processes in epithelial and non‐epithelial tissues. In cancer biology, EMPs display context-dependent functions, acting either as tumour suppressors or as promoters of tumour progression. Dysregulated expression of EMPs has been observed across diverse malignancies, with elevated levels linked to enhanced cell migration, invasion and metastatic potential via activation of small GTPases such as Rac1, and through Src/FAK signalling modules. Conversely, reduced expression of particular EMPs is associated with loss of cell‐cycle control and poorer patient outcomes in specific carcinomas. Mechanistic studies have elucidated interactions between EMPs and integrin complexes, modulation of phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) cascades, and epigenetic regulation via promoter hypermethylation. The global significance of EMPs in oncology is underscored by their emerging roles as prognostic biomarkers and as candidate targets for antibody-based imaging and therapeutics. As such, EMPs bridge basic insights into membrane protein architecture with translational opportunities for diagnosis, stratification and intervention in human cancer.

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Epithelial Membrane Proteins in Cancer Biology publication trend

The graph below shows the total number of articles in epithelial membrane proteins in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Epithelial membrane proteins (EMPs): A family of small hydrophobic proteins with four transmembrane domains involved in cell growth, adhesion and signalling.

Tetraspan proteins: Membrane proteins characterised by four transmembrane helices that organise signalling complexes in the plasma membrane.

Metastasis: The multi-stage process by which cancer cells spread from a primary tumour to establish secondary growths in distant organs.

Tumour microenvironment: The complex milieu of stromal cells, extracellular matrix and signalling molecules surrounding a tumour that influences its behaviour.

Immunohistochemistry: A laboratory technique that uses antibodies to visualise the distribution and abundance of specific proteins in tissue sections.

PI3K/Akt pathway: A key intracellular signalling cascade regulating cell survival, proliferation and metabolism, often dysregulated in cancer.

MAPK pathway: A mitogen-activated protein kinase signalling cascade that mediates responses to growth factors and stress, implicated in cell proliferation and differentiation.

References

1. Expression of EMP 1, 2, and 3 in Adrenal Cortical Neoplasm and Pheochromocytoma. International Journal of Molecular Sciences (2023).
2. Unraveling the structures, functions and mechanisms of epithelial membrane protein family in human cancers. Experimental Hematology & Oncology (2022).
3. The Pivotal Roles of the Epithelial Membrane Protein Family in Cancer Invasiveness and Metastasis. Cancers (2019).
4. Epithelial membrane protein 1 promotes tumor metastasis by enhancing cell migration via copine-III and Rac1. Oncogene (2018).
5. Epithelial Membrane Protein-2 Promotes Endometrial Tumor Formation through Activation of FAK and Src. PLOS ONE (2011).
6. Epithelial Membrane Protein-1, Peripheral Myelin Protein 22, and Lens Membrane Protein 20 Define a Novel Gene Family *. Journal of Biological Chemistry (1995).
7. The Tetraspan Protein Epithelial Membrane Protein-2 Interacts with β1 Integrins and Regulates Adhesion*. Journal of Biological Chemistry (2002).
8. Targeting EMP3 suppresses proliferation and invasion of hepatocellular carcinoma cells through inactivation of PI3K/Akt pathway. Oncotarget (2015).
9. Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway. International Journal of Molecular Sciences (2021).
10. Promoter Hypermethylation of the EMP3 Gene in a Series of 229 Human Gliomas. BioMed Research International (2013).
11. Positron Emission Tomography Imaging of Endometrial Cancer Using Engineered Anti-EMP2 Antibody Fragments. Molecular Imaging and Biology (2012).