The epithelial–mesenchymal transition (EMT) is a cellular reprogramming process that occurs during embryonic development and adult tissue homeostasis. This process involves epithelial cells acquiring a mesenchymal phenotype. Through EMT, cancer cells acquire properties associated with a more aggressive phenotype. EMT and its opposite, mesenchymal–epithelial transition (MET), have been described in more tumors over the past ten years, including colorectal cancer (CRC). When EMT is activated, the expression of the epithelial marker E-cadherin is decreased and the expression of the mesenchymal marker vimentin is raised. As a result, cells temporarily take on a mesenchymal phenotype, becoming motile and promoting the spread of tumor cells. Epithelial–mesenchymal plasticity (EMP) has become a hot issue in CRC because strong inducers of EMT (such as transforming growth factor β, TGF-β) can initiate EMT and regulate metastasis, microenvironment, and immune system resistance in CRC. In this review, we take into account the significance of EMT-MET in CRC and the impact of the epithelial cells’ plasticity on the prognosis of CRC. The analysis of connection between EMT and colorectal cancer stem cells (CCSCs) will help to further clarify the current meager understandings of EMT. Recent advances affecting important EMT transcription factors and EMT and CCSCs are highlighted. We come to the conclusion that the regulatory network for EMT in CRC is complicated, with a great deal of crosstalk and alternate paths. More thorough research is required to more effectively connect the clinical management of CRC with biomarkers and targeted treatments associated with EMT.

Angiogenesis constitutes a critical rate-limiting determinant of tumor progression in breast cancer (BC). Resistance to conventional anti-angiogenic therapies in BC highlights an unmet need to identify upstream molecular regulators coordinating malignant cell plasticity and vascular remodeling. Lemur tail kinase 3 (LMTK3) is a well-established oncogenic kinase; however, its specific role within the tumor angiogenic microenvironment remains undefined. Here, we identify LMTK3 as a context-dependent driver of angiogenesis through a mesenchymal-epithelial transition (MET) program. By integrating single-cell RNA sequencing with functional validation, we uncover a ‘Simpson’s paradox’ (where a correlation present in different groups disappears or reverses when combined): In mesenchymal-like triple-negative breast cancer (TNBC), LMTK3 promotes a pro-angiogenic, ‘partial EMT’ (p-EMT) state characterized by sustained ERK signaling and elevated secretion of angiogenic factors, including angiogenin. Conversely, in luminal-like cells, LMTK3 enforces a hyperepithelialized state that suppresses angiogenic phenotypes. Consequently, LMTK3 emerges as a central regulator of angiogenic plasticity, and its targeted inhibition offers a promising strategy to abrogate the pro-angiogenic p-EMT state and promote vascular normalization in TNBC.

The mortality associated with gastric cancer (GC) is mostly attributed to metastasis that is resistant to therapy, presenting a therapeutic challenge that frequently continues even after effective eradication of Helicobacter pylori ( H. pylori ). This paper addresses the “eradication paradox” by introducing a novel conceptual framework, the “Survival Switch” hypothesis: H. pylori infection not only induces a temporary epithelial–mesenchymal transition (EMT) but also stabilizes gastric epithelial cells in a persistent, drug-resistant “Hybrid Epithelial/Mesenchymal (Hybrid E/M) state.” We systematically outline this evolutionary trajectory through three distinct phases: (1) The Igniter: The virulence factor Cytotoxin-associated gene A (CagA) compromises junctional integrity and commandeers YAP/ZEB1 signaling to initiate plasticity; (2) The Lock: A “Hit-and-Run” mechanism establishes “epigenetic scarring,” specifically methyltransferase-like 3 (METTL3)-mediated N ⁶ -methyladenosine (m ⁶ A) modifications, that perpetuates the mesenchymal phenotype independently of the bacterial stimulus; and (3) The Niche: An inflammatory ecosystem comprising CAFs and TAMs functions as an extrinsic amplifier, creating a “fail-safe” network that reinforces the hybrid state through paracrine feedback loops. We propose a theoretical paradigm shift in clinical practice from broad-spectrum cytotoxicity to a “Wake-up and Kill” sequential strategy, employing EMT-reversing drugs to activate the survival switch and re-sensitize tumors before chemotherapy. This review presents a precise strategy for overcoming the epigenetic and stromal barriers of refractory GC by incorporating upcoming technologies like liquid biopsy for dynamic stratification and nanocarrier-based RNA delivery.

The complexity of breast cancer (BC) lung metastasis lies in the capacity of tumour cells to interact efficiently with distant organs to promote colonisation, a process that involves the sophisticated coordination of inherent cellular plasticity and the remodelling of the distant microenvironment. This review emphasises the essential function of extracellular vesicles (EVs) within this communication network. Tumour‐derived EVs (TEVs) not only induce epithelial–mesenchymal transition (EMT) by reprogramming breast cancer cell gene expression networks, thereby enhancing migratory and invasive capabilities, but also serve as a ‘vanguard’, arriving in the lungs in advance to educate stromal cells and establish a pre‐metastatic niche that facilitates breast cancer progression. This review uniquely conceptualises EV‐mediated EMT and niche formation as a synergistic and sequential biological continuum. We comprehensively examine the sorting mechanisms of EV molecular cargo, targeted delivery approaches, and hierarchical regulatory networks. Critically, we propose that the concurrent regulation of EMT and niche formation is likely driven by the synergistic action of distinct EV subpopulations rather than single ‘multitasking’ vesicles. Future investigations dissecting this heterogeneity will be pivotal for verifying this synergistic subpopulations hypothesis and establishing a theoretical basis for precise EV‐based metastasis intervention strategies.