Transitions Between Epithelial and Mesenchymal States: Acquisition of Malignant and Stem Cell Traits

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2009 Mar 6

PMID 19262571

Citations 1749

Authors

Kornelia Polyak

Robert A Weinberg

Affiliations

Soon will be listed here.

Abstract

Transitions between epithelial and mesenchymal states have crucial roles in embryonic development. Emerging data suggest a role for these processes in regulating cellular plasticity in normal adult tissues and in tumours, where they can generate multiple, distinct cellular subpopulations contributing to intratumoural heterogeneity. Some of these subpopulations may exhibit more differentiated features, whereas others have characteristics of stem cells. Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients.

Citing Articles

Cellular polarity pilots breast cancer progression and immunosuppression.

Huang J, Luo S, Shen J, Lee M, Chen R, Ma S Oncogene. 2025; .

PMID: 40057606 DOI: 10.1038/s41388-025-03324-0.

The role of ESRP1 in solid tumor development through the regulation of CD44 splicing and EMT processes.

Wang L, Zhang M, Zhao K, Yuan X, Zhao H, Liu Y Front Oncol. 2025; 15:1451130.

PMID: 40046628 PMC: 11881191. DOI: 10.3389/fonc.2025.1451130.

Impact of LIN7A silencing on U87 cell invasion and its clinical significance in glioblastoma.

Lyu X, Shi Y, Wang D, Cao X, Guo J, Huang G Sci Rep. 2025; 15(1):7212.

PMID: 40021783 PMC: 11871311. DOI: 10.1038/s41598-025-91285-5.

The Multifaceted Roles of MicroRNA-181 in Stem Cell Differentiation and Cancer Stem Cell Plasticity.

Yang C, Wang R, Hardy P Cells. 2025; 14(2.

PMID: 39851559 PMC: 11763446. DOI: 10.3390/cells14020132.

ITGAX promotes gastric cancer progression via epithelial-mesenchymal transition pathway.

Hu J, Cao J, Huang S, Chen Y Front Pharmacol. 2025; 15():1536478.

PMID: 39845786 PMC: 11750855. DOI: 10.3389/fphar.2024.1536478.

References

Zhang W, Glockner S, Guo M, Machida E, Wang D, Easwaran H . Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer. Cancer Res. 2008; 68(8):2764-72. PMC: 2823123. DOI: 10.1158/0008-5472.CAN-07-6349. View

Husemann Y, Geigl J, Schubert F, Musiani P, Meyer M, Burghart E . Systemic spread is an early step in breast cancer. Cancer Cell. 2008; 13(1):58-68. DOI: 10.1016/j.ccr.2007.12.003. View

Guo Y, Pakneshan P, Gladu J, Slack A, Szyf M, Rabbani S . Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion. J Biol Chem. 2002; 277(44):41571-9. DOI: 10.1074/jbc.M201864200. View

Chaffer C, Thompson E, Williams E . Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs. 2007; 185(1-3):7-19. DOI: 10.1159/000101298. View

Filipowicz W, Bhattacharyya S, Sonenberg N . Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet. 2008; 9(2):102-14. DOI: 10.1038/nrg2290. View

Elloul S, Elstrand M, Nesland J, Trope C, Kvalheim G, Goldberg I . Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer. 2005; 103(8):1631-43. DOI: 10.1002/cncr.20946. View

Cannito S, Novo E, Compagnone A, di Bonzo L, Busletta C, Zamara E . Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis. 2008; 29(12):2267-78. DOI: 10.1093/carcin/bgn216. View

Ma L, Teruya-Feldstein J, Weinberg R . Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007; 449(7163):682-8. DOI: 10.1038/nature06174. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

10.

Honeth G, Bendahl P, Ringner M, Saal L, Gruvberger-Saal S, Lovgren K . The CD44+/CD24- phenotype is enriched in basal-like breast tumors. Breast Cancer Res. 2008; 10(3):R53. PMC: 2481503. DOI: 10.1186/bcr2108. View

11.

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

12.

Mani S, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N . Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A. 2007; 104(24):10069-74. PMC: 1891217. DOI: 10.1073/pnas.0703900104. View

13.

Yates C, Shepard C, Stolz D, Wells A . Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. Br J Cancer. 2007; 96(8):1246-52. PMC: 2360137. DOI: 10.1038/sj.bjc.6603700. View

14.

Sheridan C, Kishimoto H, Fuchs R, Mehrotra S, Bhat-Nakshatri P, Turner C . CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 2006; 8(5):R59. PMC: 1779499. DOI: 10.1186/bcr1610. View

15.

Plass C . Cancer epigenomics. Hum Mol Genet. 2002; 11(20):2479-88. DOI: 10.1093/hmg/11.20.2479. View

16.

Ozdamar B, Bose R, Barrios-Rodiles M, Wang H, Zhang Y, Wrana J . Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science. 2005; 307(5715):1603-9. DOI: 10.1126/science.1105718. View

17.

Dunbier A, Guilford P . Hereditary diffuse gastric cancer. Adv Cancer Res. 2001; 83:55-65. DOI: 10.1016/s0065-230x(01)83002-5. View

18.

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C . let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007; 131(6):1109-23. DOI: 10.1016/j.cell.2007.10.054. View

19.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

20.

Graff J, Gabrielson E, Fujii H, Baylin S, Herman J . Methylation patterns of the E-cadherin 5' CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem. 2000; 275(4):2727-32. DOI: 10.1074/jbc.275.4.2727. View