Sabyasachi Parija, a fourth-year undergraduate student at the Indian Institute of Science Education and Research Berhampur, is exploring the fascinating world of epithelial-to-mesenchymal transition (EMT), a critical process in cancer biology. In this opinion article, Sabyasachi reflects on the molecular intricacies of EMT and its role in cancer progression, sharing his thoughts on why understanding this process could be key to unlocking new strategies in cancer treatment and research.
Today, if research on cancer is mentioned, it is often assumed that the goal is to find a cure. While the discovery of a cure for cancer is regarded as a remarkable achievement for both humanity and the scientific world, the question remains — is a cure for cancer merely a myth?
Undoubtedly, significant progress has been made in cancer research rapidly over the years. As human curiosity cannot be constrained, therapeutic approaches to combat this disease are being explored by researchers in pursuit of solutions that may one day be found to be effective.
In our rapidly evolving world, if a search is conducted in PubMed or within any scientific journal database for cancer-related studies, it might be observed that 20 – 30 articles are added daily. This shows how vast the field is.
Many amateur or learner students like me are often found in the first year of their undergraduate courses. A goal such as becoming a cancer biologist and solving the problem of finding a cure for cancer is often set — even before understanding what cancer truly is. Questions such as how cancer spreads from one body part to another or what a tumour actually is are frequently left unanswered at that stage.
By the time undergraduate studies are completed, some basic knowledge about cancer is usually acquired, regardless of the specific course pursued. . When cancer is chosen to be the research topic, the first question that must be addressed is: What aspect of cancer is to be studied? — because cancer is a vast and complex subject. This realisation was brought to me during my coursework when I was introduced to a cancer biology course conducted by R Selvi Bharathavikru. Through her teaching, many concepts in cancer biology — from the p53 gene and RB gene functions to tyrosine kinase inhibitors and cancer stem cells — were explained. However, the topic that most fascinated me during the course was presented as EMT.
EMT stands for epithelial-to-mesenchymal transition. While the acronym itself is not always explained, in science it is important that such terms are understood clearly. EMTs are the acquisition of mesenchymal features from epithelial cells that occur during certain biological processes.
EMT in cancer: The double-edged sword
Highlights in cancer research today are shedding light on veritable mysteries that seem stranger than fiction. Among these paradoxical cellular properties, EMT undoubtedly interferes as a double-edged sword. While EMT is essential for life, its role in metastasis — one of the darkest aspects of cancer progression — makes it a molecular paradox that must be carefully examined and understood.
EMT: The shape-shifter of cells
Imagine epithelial cells as disciplined citizens forming tight-knit communities. During EMT, these cells shed their communal bonds and adopt a rebellious, mobile form — mesenchymal cells. This ability to transform is crucial for embryonic development and wound healing. However, in cancer, EMT enables cells to become invasive , spreading disease across the body. In scientific words, EMT is defined as the transition of epithelial cells into mesenchymal ones, but the first step involves breaking down the tight junction that keeps epithelial cells anchored in place.
EMT’s role in cancer metastasis
Metastasis, responsible for over 90% of cancer deaths, relies heavily on EMTs. Through this process, tumour cells gain motility, detach from the primary tumour, and invade new areas via the blood or lymphatic systems. Interestingly, these cells can revert to their original epithelial state at their destination through the mesenchymal-epithelial transition (MET), forming new tumours.
The puppet masters of EMT
Behind EMT’s transformative power lies a cast of molecular actors. Proteins and transcription factors like TWIST, Snail, and ZEB1 (Zinc finger E‑box binding homeobox 1) act as directors (regulators), silencing genes that uphold epithelial traits and activating genes for mesenchymal behaviour. This includes reducing E‑cadherin, the “glue” that holds cells together, and increasing N‑cadherin, which enhances cell mobility. Signalling molecules like TGF‑β (transforming growth factor beta) trigger internal changes that further amplify EMT’s effects. In low oxygen levels, HIF-1α (hypoxia-inducible factor 1‑alpha) is activated, increasing TWIST expression and fuelling EMT and metastasis.
EMT and cancer stem cells (CSCs): The deadly duo
EMT not only spreads cancer but also grants cells stem-like properties, making them self-renewing and resilient — key cancer stem cells (CSCs) traits. This ability to initiate new tumours makes EMT a critical target for cancer therapies.
The dark side of EMT
While EMT plays a vital role in natural processes such as organ development and wound healing, its involvement in cancer reveals a far more sinister side. It arms cancer cells with mechanisms to evade the immune system and resist treatment, posing significant challenges for oncologists globally. Every pathway and signalling mechanism involved in EMT presents a potential therapeutic target, but the complexity of these networks makes them extremely difficult to tackle.
Rewriting the cancer playbook
Researchers are exploring ways to counteract EMT’s dark role:
Inhibiting EMT drivers: Blocking transcription factors like TWIST or signalling pathways such as TGF‑β could prevent cells from becoming invasive.
Encouraging MET: Reversing EMT at secondary sites may make cancer cells less mobile and more vulnerable.
Targeting hypoxia: Reducing tumour oxygen deprivation could slow EMT-driven metastasis.
Immune therapies: Enhancing immune responses may counteract EMT’s cloaking abilities.
The future of EMT research
The dual nature of EMT — supporting development while also promoting disease—highlights the inherent complexity of biology. By effectively targeting this process, cancer progression could be halted. This is not merely about prolonging life, but about restoring its quality, as science continues to transform once- fictional mysteries into life-saving breakthroughs. In the ever-evolving narrative of cancer, EMT remains both villain and a key player. A deeper understanding of this process may prove to be the turning point in our battle against one of the world’s most insidious diseases.
Mohit Kumar Jolly, Assistant Professor at the Centre for BioSystems Science and Engineering (BSSE) at IISc Bangalore, is an expert in the field of epithelial-mesenchymal transition (EMT) and cancer metastasis. His research focuses on understanding the regulatory dynamics of EMT and identifying phenotypic states that play a crucial role in cancer progression. On the evolving understanding of EMT, he states:
EMT was initially thought of as a binary process with cells acquiring epithelial or mesenchymal state. We predicted over a decade ago based on mathematical modeling of interactions among different EMT and MET regulators that cells could also stably acquire hybrid epithelial/mesenchymal (E/M) phenotypes that can integrate cell-cell adhesion and migration traits, enabling collective or clustered cell migration. Similar predictions have been made since by many other expert colleagues, and these hybrid E/M phenotypes have now been reported in vitro and in vivo across many cancer types. These hybrid E/M phenotypes are thought of as the fittest for metastasis, and targeting them therapeutically is an active research area in the community now.”
There is yet to be discovered and discussed, and our understanding of this complex process will continue to increase with time.
References
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