Cited by 80Cancer Cells and MetastasisTGF-β signaling in diseasesMechanisms of cancer metastasis

Epithelial-mesenchymal transition orchestrates tumor microenvironment: Current perceptions and challenges

Open access
Xie, Yuqi, Wang, Xuan, Wang, Wenquan, Pu, Ning, Liu, Liang·2025·Journal of Translational Medicine

Abstract

The epithelial-mesenchymal transition (EMT) is a critical process in cancer progression, facilitating tumor cells to develop invasive traits and augmenting their migratory capabilities. EMT is primed by tumor microenvironment (TME)-derived signals, whereupon cancer cells undergoing EMT in turn remodel the TME, thereby modulating tumor progression and therapeutic response. This review discusses the mechanisms by which EMT coordinates TME dynamics, including secretion of soluble factors, direct cell contact, release of exosomes and enzymes, as well as metabolic reprogramming. Recent evidence also indicates that cells undergoing EMT may differentiate into cancer-associated fibroblasts, thereby establishing themselves as functional constituents of the TME. Elucidating the relationship between EMT and the TME offers novel perspectives for therapeutic strategies to enhance cancer treatment efficacy. Although EMT-directed therapies present significant therapeutic potential, the current lack of effective targeting approaches-attributable to EMT complexity and its microenvironmental context dependency-underscores the necessity for mechanistic investigations and translational clinical validation.

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  • Epithelial-to-mesenchymal transition (EMT) plays a critical role in driving phenotypic diversity in solid tumors by suppressing epithelial markers such as E-cadherin and upregulating mesenchymal markers like vimentin and N-cadherin.

    “In addition to these models, EMT plays a critical role in driving phenotypic diversity in solid tumors. Through EMT, epithelial cancer cells undergo a dynamic reprogramming process that suppresses epithelial markers, such as E-cadherin, while upregulating mesenchymal markers, like vimentin and N-cadherin [130,131].”

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Research works printed but not linked: 2

  1. [2]Nieto MA, Huang RY, Jackson RA, Thiery JP. EMT: 2016. Cell. 2016;166(1):21–45. 27368099
  2. [70]Butcher S, Arney KL, Cook GP. MAFA-L, an ITIM-containing receptor encoded by the human NK cell gene complex and expressed by basophils and NK cells. Eur J Immunol. 1998;28(11):3755–62. 9842918

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Authors
Xie, Y., Wang, X., Wang, W., Pu, N., & Liu, L.
Affiliations
Fudan University (CN)
Corresponding author
Liu, Liang
Venue
Journal of Translational Medicine
Published
2025-04-02
Volume
23
Issue
1
Pages
386-386
ISSN
1479-5876 (ISSN-L)
OpenAlex
W4409124165
Cited by
80
References
182
Citations by year
2026: 51 · 2025: 29
FWCI
9.39
Type
journal article
Language
en
Open access
Locations
  • Journal of Translational Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82473459, 82303443, 82273382, 82272929, 82103409, 82103417)
  • Program of Shanghai Academic Research Leader (23XD1400600)
  • Science and Technology Commission of Shanghai Municipality (24SF1900300)
  • Shanghai Municipal Health Commission (20244Y0023, 201940019)
  • Beijing Xisike Clinical Oncology Research Foundation (Y-2022METAZQN-0003, Y-Gilead2024-PT-0002, Y-HR2022MS-0251, Y-HR2022QN-0085)
  • Yunnan Provincial Science and Technology Department (202305AF150148)
  • Shanghai Health and Medical Development Foundation
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Keywords
epithelial-mesenchymal transition, tumor microenvironment, tumor progression, tumor invasion, cell migration, exosomes, metabolic reprogramming, cancer-associated fibroblasts, soluble factors, cell-cell contact, therapeutic targeting
MeSH terms
Animals, Humans, Neoplasms, Epithelial-Mesenchymal Transition, Tumor Microenvironment

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