Epithelial-Mesenchymal Transition in Cancer Biology

Epithelial–mesenchymal transition (EMT) is a reversible cellular programme in which epithelial cells lose polarity and cell–cell adhesion, acquiring mesenchymal traits including motility and invasiveness. In cancer, EMT underpins metastasis, therapeutic resistance and the acquisition of stem-like properties. A conserved network of signalling pathways—most notably transforming growth factor-β (TGF-β), WNT/β-catenin, Notch and PI3K/AKT—drives transcriptional changes mediated by factors such as SNAIL, SLUG and TWIST. EMT is dynamic and can generate hybrid epithelial/mesenchymal states that facilitate collective cell migration and survival in the circulation as clusters of circulating tumour cells. Equally, reversal through mesenchymal–epithelial transition (MET) supports secondary colonisation. The tumour microenvironment, including fibroblasts, immune cells and extracellular matrix remodelling, further modulates EMT plasticity. Understanding EMT’s molecular underpinnings has profound implications for anticipating metastasis, overcoming drug resistance and developing targeted interventions.

Research from Nature Portfolio

Recent studies have uncovered a key regulator of EMT-associated chemoresistance: the small GTPase RHOJ. In models of spontaneous tumour EMT, RHOJ expression enhances the DNA-damage response and repair following chemotherapy by coordinating nuclear actin dynamics, and its inhibition restores chemosensitivity. This finding elucidates how EMT cells survive cytotoxic stress and suggests novel strategies that combine actin polymerisation inhibitors with standard regimens. Complementing mechanistic insights, a consensus statement has standardised EMT nomenclature and definitions, clarifying criteria for epithelial, mesenchymal and hybrid phenotypes. The guidelines harmonise marker panels and functional assays across developmental, fibrotic and oncogenic EMT models, thereby facilitating cross-disciplinary research and improving the comparability of experimental data.

Epithelial-Mesenchymal Transition in Cancer Biology publication trend

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

Technical terms

Epithelial–Mesenchymal Transition (EMT): A cellular programme in which epithelial cells acquire motile, invasive mesenchymal characteristics.

Mesenchymal–Epithelial Transition (MET): The reverse process of EMT, restoring epithelial traits to mesenchymal-like cells, critical for metastatic colonisation.

RHOJ: A small GTPase preferentially expressed in EMT cancer cells that regulates DNA repair and confers chemotherapy resistance.

E-cadherin: An epithelial adhesion molecule whose downregulation is a hallmark of EMT.

N-cadherin: A mesenchymal adhesion protein upregulated during EMT, facilitating increased motility.

Transforming growth factor-β (TGF-β): A cytokine that orchestrates EMT by activating transcription factors and downstream signalling networks.

Cancer stem cell (CSC): A tumour subpopulation with self-renewal capabilities, often associated with EMT-driven therapeutic resistance.

References

1. Cancer stem cells: advances in knowledge and implications for cancer therapy. Signal Transduction and Targeted Therapy (2024).
2. RHOJ controls EMT-associated resistance to chemotherapy. Nature (2023).
3. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduction and Targeted Therapy (2020).
4. Guidelines and definitions for research on epithelial–mesenchymal transition. Nature Reviews Molecular Cell Biology (2020).
5. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells (2019).
6. TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis. International Journal of Molecular Sciences (2019).
7. Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis. Frontiers in Oncology (2015).