Cellular and Molecular Life Sciences

, Volume 69, Issue 20, pp 3429–3456 | Cite as

EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness

  • Ester Sánchez-Tilló
  • Yongqing Liu
  • Oriol de Barrios
  • Laura Siles
  • Lucia Fanlo
  • Miriam Cuatrecasas
  • Douglas S. Darling
  • Douglas C. Dean
  • Antoni Castells
  • Antonio Postigo
Review

Abstract

Cancer is a complex multistep process involving genetic and epigenetic changes that eventually result in the activation of oncogenic pathways and/or inactivation of tumor suppressor signals. During cancer progression, cancer cells acquire a number of hallmarks that promote tumor growth and invasion. A crucial mechanism by which carcinoma cells enhance their invasive capacity is the dissolution of intercellular adhesions and the acquisition of a more motile mesenchymal phenotype as part of an epithelial-to-mesenchymal transition (EMT). Although many transcription factors can trigger it, the full molecular reprogramming occurring during an EMT is mainly orchestrated by three major groups of transcription factors: the ZEB, Snail and Twist families. Upregulated expression of these EMT-activating transcription factors (EMT-ATFs) promotes tumor invasiveness in cell lines and xenograft mice models and has been associated with poor clinical prognosis in human cancers. Evidence accumulated in the last few years indicates that EMT-ATFs also regulate an expanding set of cancer cell capabilities beyond tumor invasion. Thus, EMT-ATFs have been shown to cooperate in oncogenic transformation, regulate cancer cell stemness, override safeguard programs against cancer like apoptosis and senescence, determine resistance to chemotherapy and promote tumor angiogenesis. This article reviews the expanding portfolio of functions played by EMT-ATFs in cancer progression.

Keywords

Cancer stem cells E-cadherin EMT Invasiveness Metastasis Snail1 Snail2 Tumorigenesis Twist1 Twist2 ZEB1 ZEB2 

Abbreviations

bHLH

Basic helix loop helix

CSC

Cancer stem cells

EMT

Epithelial-to-mesenchymal transition

EMT-ATF

EMT-activating transcription factors

HNSCC

Head and neck squamous cell carcinoma

MET

Mesenchymal-to-epithelial transition

NSCLC

Non-small cell lung carcinoma

Notes

Acknowledgments

We apologize to those researchers whose relevant work was cited only indirectly through reviews because of space limitations. Experimental work was conducted by E.S.T., Y.L., O.d.B., L.S. and L.F.. M.C. and A.C. identified tissue samples and/or advised in the interpretation of immunostaining. A.P. wrote the article and all authors contributed to its critical revision. Comments on the manuscript by E.C. Vaquero are also greatly appreciated. Tissue samples for Fig. 4 were obtained from IDIBAPS’ Tumor Bank. Work in A.P.’s laboratory was funded by grants from Olga Torres Foundation, AVON Cosmetics SAU, Spanish Association Against Cancer (AECC), Spanish Ministry of Economy and Competitiveness (formerly of Science and Innovation, BFU2007-60302, BFU2010-15163), La Caixa Foundation, and the European Commission. E.S.T.’s salary is funded by CIBERehd. O.d.B. and L.S. are recipients of PhD scholarships from the Spanish Ministry of Education, Culture and Sports (FPU Program). L.S.’s salary was previously funded by AECC.

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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Ester Sánchez-Tilló
    • 1
    • 2
  • Yongqing Liu
    • 3
    • 4
  • Oriol de Barrios
    • 1
  • Laura Siles
    • 1
  • Lucia Fanlo
    • 1
    • 5
  • Miriam Cuatrecasas
    • 6
  • Douglas S. Darling
    • 7
  • Douglas C. Dean
    • 3
    • 4
  • Antoni Castells
    • 2
    • 8
  • Antonio Postigo
    • 1
    • 2
    • 3
    • 9
  1. 1.Group of Transcriptional Regulation of Gene Expression, Department of Oncology and HematologyIDIBAPSBarcelonaSpain
  2. 2.CIBERehd (Gastrointestinal and Pancreatic Oncology)IDIBAPSBarcelonaSpain
  3. 3.James Graham Brown Cancer CenterLouisville Health Science CenterLouisvilleUSA
  4. 4.Department of Ophthalmology and Birth Defects CenterLouisville Health Science CenterLouisvilleUSA
  5. 5.Master Program in Biomedical ResearchUniversity Pompeu FabraBarcelonaSpain
  6. 6.Department of PathologyHospital Clinic and IDIBAPS’ Tumor BankBarcelonaSpain
  7. 7.Department of Oral Health and Rehabilitation, Center for Genetics and Molecular MedicineUniversity of LouisvilleLouisvilleUSA
  8. 8.Institute of Digestive and Metabolic DiseasesHospital ClinicBarcelonaSpain
  9. 9.ICREABarcelonaSpain

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