Key Takeaways
- EMT (epithelial-mesenchymal transition) is a biological process in which stationary epithelial cells — the cells lining organs and body surfaces — transform into mobile, stem cell-like mesenchymal cells that can migrate throughout the body.
- EMT is normal and essential during fetal development, but when it is activated after birth, it can cause epithelial cells to become cancerous and invasive — a process linked to multiple aggressive cancers, including mesothelioma.
- Researchers are investigating EMT as a potential mechanism by which asbestos actually causes mesothelioma — filling in a critical gap in scientific understanding between asbestos exposure and cancer development.
- A 2022 study identified a mesothelioma-specific EMT gene signature — four genes (COL5A2, ITGAV, SPARC, and ACTA2) that are overexpressed in mesothelioma patients. This gene signature may explain therapy resistance, metastasis tendencies, and prognosis.
- The EMT gene signature could become a target for novel therapies, including gene therapy — treatments designed to silence or modify the specific genes driving mesothelioma growth.
What is the Process of EMT?
“EMT” stands for epithelial-mesenchymal transition, which is a process that usually occurs in fetal development. In this process, epithelial cells (which are the cells covering most of the body’s surfaces, like the skin, organs, and blood vessels) become mobile and invasive, like mesenchymal stem cells. Usually, epithelial cells are tethered to their fellow epithelial cells by way of cellular adhesion; this gives them their barrier-like qualities. This cellular adhesion is facilitated by cellular polarity, which is the tendency of cells to unevenly disperse their organelles and proteins. Cells have complementary shapes, thanks to the phenomenon of cellular polarity. When a signal or protein disrupts this polarity, epithelial cells break free from their anchoring spot; from there, they can migrate around the body and impart a similar disruption in other epithelial tissues (hence, the “mesenchymal” transition).
How does EMT Intersect with Mesothelioma Growth?
In fetal development, EMT allows epithelial cells to act like stem cells, which helps establish different epithelial membranes. EMT is absolutely critical in utero; however, if it’s activated afterwards, then epithelial cells can become cancerous. EMT is known to be implicated in other cancers, so it makes sense to research it in the context of mesothelioma.
Mesothelioma is causally linked to asbestos exposure, but scientists don’t know the mechanisms by which asbestos causes mesothelioma. There are several theories, and the actual process of carcinogenesis has several factors—immunosuppression, genetic mutations, etc. But EMT is now being investigated as a.) a mechanism of carcinogenesis; b.) a way that asbestos is implicated in mesothelioma; and c.) a target for new treatments.
A recent study (2022) investigated the gene signature, or the characteristic expression, of EMT-related genes. The researchers established a panel of EMT genes overexpressed in mesothelioma patients: COL5A2, ITGAV, SPARC and ACTA2. In their discussion, the researchers noted that the expression of EMT genes could contribute to mesothelioma’s resistance to therapy, prognosis, and tendency to metastasize. They also suggested that mesothelioma’s EMT gene signature could be a legitimate target for novel therapies, including gene therapy.
If you or a loved one has been diagnosed with mesothelioma, please call 1 (800)-505-6000 or fill out our contact form. We are here to help you navigate the legal process of filing a claim to receive compensation for your mesothelioma diagnosis. We help mesothelioma victims and their families in Pennsylvania.
Frequently Asked Questions
What is EMT (epithelial-mesenchymal transition)?
EMT is a biological process in which epithelial cells — the cells that line the surfaces of organs, skin, and blood vessels — lose their adhesion to neighboring cells and transform into mobile, stem cell-like mesenchymal cells. Normally, epithelial cells are tightly bound to each other, forming protective barriers. During EMT, signals or proteins disrupt this binding, allowing the cells to break free and migrate to other parts of the body. EMT is a normal and critical process during fetal development, but when it is reactivated in adulthood, it can lead to cancer.
How does EMT contribute to mesothelioma growth?
When EMT is activated in adult mesothelial cells, those cells can break away from the tissue lining, migrate through the body, and become cancerous and invasive. EMT has been established as a contributor to several aggressive cancers, and researchers are now investigating it as a key mechanism in mesothelioma specifically. EMT may help explain three critical aspects of the disease: how asbestos exposure leads to cancer (carcinogenesis), why mesothelioma is so resistant to treatment, and why the cancer tends to spread (metastasize) aggressively.
What is the mesothelioma-specific EMT gene signature?
A 2022 study identified a panel of four genes that are overexpressed in mesothelioma patients and are associated with the EMT process:
- COL5A2
- ITGAV
- SPARC
- ACTA2
Together, these four genes form a “gene signature” that is characteristic of EMT-driven mesothelioma. Researchers found that the expression of these genes may contribute to therapy resistance, metastasis, and prognosis — meaning they could be used to predict how the cancer will behave and how it might respond to treatment.
Could EMT explain why asbestos causes mesothelioma?
Potentially. While scientists know that asbestos exposure is the primary cause of mesothelioma, the exact biological mechanism — how inhaled asbestos fibers trigger cancer — is still not fully understood. EMT is now being investigated as one possible pathway. Asbestos fibers may disrupt the cellular polarity and adhesion mechanisms that keep epithelial cells in place, triggering the EMT process and causing cells to become migratory and cancerous. If confirmed, this would fill in a critical gap between “asbestos exposure happened” and “mesothelioma developed.”
How does EMT relate to the different mesothelioma cell subtypes?
EMT provides a scientific framework for understanding the three cell subtypes:
- Epithelioid mesothelioma — cells that have retained more of their original epithelial characteristics (stationary, clustered, defined shape). These have undergone less EMT, which is part of why they grow more slowly and respond better to treatment.
- Sarcomatoid mesothelioma — cells that have undergone a more complete EMT, becoming highly mobile, irregularly shaped, and aggressive. This explains their rapid spread and treatment resistance.
- Biphasic mesothelioma — contains cells at different stages of the EMT spectrum, which is why the ratio of epithelioid to sarcomatoid cells determines prognosis.
Understanding EMT helps explain why these subtypes behave so differently — they may represent different stages of the same cellular transformation process.
Could the EMT gene signature be used to develop new treatments?
Yes. The researchers who identified the mesothelioma-specific EMT gene signature (COL5A2, ITGAV, SPARC, ACTA2) suggested that these genes could become legitimate targets for novel therapies, including gene therapy. If treatments could silence or modify the expression of these genes, it might be possible to slow or prevent the EMT process — stopping mesothelioma cells from becoming migratory and invasive. This approach could also address one of the biggest challenges in treatment: therapy resistance.
What should I do if I’ve been diagnosed with mesothelioma?
If you or a loved one has been diagnosed with mesothelioma, understanding the full range of treatment options — including emerging research into EMT-targeted therapies and other clinical trials — is an important step. For information about your legal options, call (800) 505-6000 or fill out our contact form for a free consultation.
Sources:
National Library Of Medicine 1
National Library Of Medicine 2
