Event: 1650

Key Event Title


Epithelial-mesenchymal transition

Short name


Epithelial-mesenchymal transition

Biological Context


Level of Biological Organization

Cell term


Cell term

Organ term


Organ term

Key Event Components


Process Object Action

Key Event Overview

AOPs Including This Key Event


AOP Name Role of event in AOP
Wnt activation leading to cancer malignancy KeyEvent



Taxonomic Applicability


Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI

Life Stages


Life stage Evidence
All life stages High

Sex Applicability


Term Evidence
Unspecific High

Key Event Description


•Epithelial-mesenchymal transition (EMT) is a phenomenon in which the cells transit from epithelial-like into mesenchymal-like phenotypes (S. Tanabe, 2017; Shihori Tanabe, Komatsu, Kazuhiko, Yokozaki, & Sasaki, 2015). In cancer, cells exhibiting EMT features contribute into the metastasis and drug resistance.

•It is known that D-2-hydroxyglurate induces EMT(Guerra et al., 2017; Jia, Park, Jung, Levine, & Kaipparettu, 2018; Mishra et al., 2018; Sciacovelli & Frezza, 2017). D-2-hydroxyglurate, an inhibitor of Jumonji-family histone demethylase, increased the trimethylation of histone H3 lysine 4 (H3K4) in the promoter region of the ZEB1, followed by the induction of EMT (Colvin et al., 2016).

•Wnt5a induces EMT and metastasis in non-small-cell lung cancer (Wang, Tang, Gong, Zhu, & Liu, 2017).

•EMT is related to Wnt/beta-catenin signaling and important for cancer (S. Tanabe, Kawabata, Aoyagi, Yokozaki, & Sasaki, 2016)

•TGFbeta induces EMT (Wendt, Smith, & Schiemann, 2010).

How It Is Measured or Detected


  • TGFbeta induces EMT in vitro (Willis et al., 2005).
  • EMT can be detected by immunostaining with pro-surfactant protein-C (pro-SPC) and N-cadherin in idiopathic pulmonary fibrosis (IPF) lung in vivo (Kim et al., 2006).
  • TGFbeta induces EMT, which can be detected by immunostaining with vimentin in lung aloevela in vivo (Kim et al., 2006).

Domain of Applicability


EMT is induced in cancer and involved in cancer metastasis in Homo sapiens (Suarez-Carmona, Lesage, Cataldo, & Gilles, 2017) (Du & Shim, 2016).

Evidence for Perturbation by Stressor


GOLPH3 induces EMT (Sun et al., 2017).


LiCl induces EMT (Fang et al., 2018).


D-2-hydroxyglutarate induces EMT (Colvin et al., 2016).



Colvin, H., Nishida, N., Konno, M., Haraguchi, N., Takahashi, H., Nishimura, J., . . . Ishii, H. (2016). Oncometabolite D-2-Hydroxyglurate Directly Induces Epithelial-Mesenchymal Transition and is Associated with Distant Metastasis in Colorectal Cancer. Sci Rep, 6, 36289. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27824159. doi:10.1038/srep36289

Du, B., & Shim, J. S. (2016). Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer. Molecules, 21(7). Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27455225. doi:10.3390/molecules21070965

Fang, C. X., Ma, C. M., Jiang, L., Wang, X. M., Zhang, N., Ma, J. N., . . . Zhao, Y. D. (2018). p38 MAPK is Crucial for Wnt1- and LiCl-Induced Epithelial Mesenchymal Transition. Curr Med Sci, 38(3), 473-481. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30074215. doi:10.1007/s11596-018-1903-4

Guerra, F., Guaragnella, N., Arbini, A. A., Bucci, C., Giannattasio, S., & Moro, L. (2017). Mitochondrial Dysfunction: A Novel Potential Driver of Epithelial-to-Mesenchymal Transition in Cancer. Front Oncol, 7, 295. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29250487. doi:10.3389/fonc.2017.00295

Jia, D., Park, J. H., Jung, K. H., Levine, H., & Kaipparettu, B. A. (2018). Elucidating the Metabolic Plasticity of Cancer: Mitochondrial Reprogramming and Hybrid Metabolic States. Cells, 7(3). Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29534029. doi:10.3390/cells7030021

Kim, K. K., Kugler, M. C., Wolters, P. J., Robillard, L., Galvez, M. G., Brumwell, A. N., . . . Chapman, H. A. (2006). Alveolar epithelial cell mesenchymal transition develops <em>in vivo</em> during pulmonary fibrosis and is regulated by the extracellular matrix. Proceedings of the National Academy of Sciences, 103(35), 13180. Retrieved from http://www.pnas.org/content/103/35/13180.abstract. doi:10.1073/pnas.0605669103

Mishra, P., Tang, W., Putluri, V., Dorsey, T. H., Jin, F., Wang, F., . . . Ambs, S. (2018). ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming. J Clin Invest, 128(1), 323-340. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29202474. doi:10.1172/JCI93815

Sciacovelli, M., & Frezza, C. (2017). Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer. FEBS J, 284(19), 3132-3144. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28444969. doi:10.1111/febs.14090

Suarez-Carmona, M., Lesage, J., Cataldo, D., & Gilles, C. (2017). EMT and inflammation: inseparable actors of cancer progression. Mol Oncol, 11(7), 805-823. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28599100. doi:10.1002/1878-0261.12095

Sun, J., Yang, X., Zhang, R., Liu, S., Gan, X., Xi, X., . . . Sun, Y. (2017). GOLPH3 induces epithelial-mesenchymal transition via Wnt/beta-catenin signaling pathway in epithelial ovarian cancer. Cancer Med, 6(4), 834-844. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28332316. doi:10.1002/cam4.1040

Tanabe, S. (2017). Molecular markers and networks for cancer and stem cells. J Embryol Stem Cell Res, 1(1).

Tanabe, S., Kawabata, T., Aoyagi, K., Yokozaki, H., & Sasaki, H. (2016). Gene expression and pathway analysis of CTNNB1 in cancer and stem cells. World J Stem Cells, 8(11), 384-395. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27928465. doi:10.4252/wjsc.v8.i11.384

Tanabe, S., Komatsu, M., Kazuhiko, A., Yokozaki, H., & Sasaki, H. (2015). Implications of epithelial-mesenchymal transition in gastric cancer. Translational Gastrointestinal Cancer, 4(4), 258-264. Retrieved from http://tgc.amegroups.com/article/view/6996.

Wang, B., Tang, Z., Gong, H., Zhu, L., & Liu, X. (2017). Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer. Biosci Rep, 37(6). Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29054966. doi:10.1042/BSR20171092

Wendt, M. K., Smith, J. A., & Schiemann, W. P. (2010). Transforming growth factor-beta-induced epithelial-mesenchymal transition facilitates epidermal growth factor-dependent breast cancer progression. Oncogene, 29(49), 6485-6498. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20802523. doi:10.1038/onc.2010.377

Willis, B. C., Liebler, J. M., Luby-Phelps, K., Nicholson, A. G., Crandall, E. D., du Bois, R. M., & Borok, Z. (2005). Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol, 166(5), 1321-1332. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15855634.