API

Event: 1650

Key Event Title

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Epithelial-mesenchymal transition, induced

Short name

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Epithelial-mesenchymal transition, induced

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Cell term
cell


Organ term

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Organ term
organ


Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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

Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI

Life Stages

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Life stage Evidence
All life stages High

Sex Applicability

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Term Evidence
Unspecific High

Key Event Description

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•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

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  • 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

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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

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


LiCl

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


D-2-hydroxyglutarate

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


References

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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.