Novità, Oncologia

EMT (Epithelial–Mesenchymal Transition)

Hits: 4

La transizione epiteliale-mesenchimale (EMT) è un processo mediante il quale le cellule epiteliali perdono la loro polarità cellulare e l’adesione cellula-cellula e acquisiscono proprietà migratorie e invasive per diventare cellule staminali mesenchimali.

Le cellule epiteliali sono strettamente collegati tra loro da giunzioni strette e hanno una polarità apico-basale

Le cellule mesenchimali, invece, sono prive di questa polarizzazione, hanno una morfologia a forma di fuso e interagiscono tra loro solo attraverso punti focali.

Le cellule mesenchimali sono cellule stromali totipotenti  che possono differenziarsi in una varietà di tipi di cellule. 

L’EMT è essenziale per numerosi processi di sviluppo tra cui la formazione del mesoderma e la formazione del tubo neurale nell’embrione. È stato anche dimostrato che l’EMT si verifica nella guarigione delle ferite, nella fibrosi degli organi.

L’EMT e la sua transizione inversa MET sono fondamentali nel processo di chemioresistenza e diffusione delle metastasi nella progressione del cancro L’EMT è associata alla progressiva ridistribuzione o sottoregolazione delle proteine ​​della giunzione specifiche delle cellule epiteliali apicali e basolaterali, come la E-caderina e la citocheratina, e la nuova espressione di molecole mesenchimali, come la vimentina e la N-caderina.

References:

  1. Creighton, C., Chang, J. and Rosen, J. (2010). Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer. Journal of Mammary Gland Biology and Neoplasia, 15(2), pp.253-260. https://doi.org/10.1007/s10911-010-9173-1
  2. Diepenbruck, M. and Christofori, G. (2016). Epithelial–mesenchymal transition (EMT) and metastasis: yes, no, maybe?. Current Opinion in Cell Biology, 43, pp.7-13. https://doi.org/10.1016/j.ceb.2016.06.002
  3. Kalluri, R. and Weinberg, R. (2009). The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation, 119(6), pp.1420-1428. https://doi.org/10.1172/JCI39104
  4. Savagner, P. (2010). The epithelial-mesenchymal transition (EMT) phenomenon. Annals of Oncology, 21(Supplement 7), pp.vii89-vii92. https://doi.org/10.1172/JCI39104
  5. (2014). Epithelial Cells – an overview. Handbook of Nanosafety. https://www.sciencedirect.com/topics/neuroscience/epithelial-cells.
  6. Zhou, P., Li, B., Liu, F., Zhang, M., Wang, Q., Liu, Y., Yao, Y. and Li, D. (2017). The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer. Molecular Cancer, 16(1). https://dx.doi.org/10.1186%2Fs12943-017-0624-9
  7. Ozolos RF. Treatment goals in ovarian cancer. Int J Gynecol Cancer. 2005;15:3–11. 
  8. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7:131–142. doi: 10.1038/nrm1835. 
  9. Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW. Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol. 2007;213:374–383. 
  10. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14:818–829. 
  11. Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol. 2008;19:294–308. 
  12. Grunert S, Jechlinger M, Beug H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 2003;4:657–665. 
  13. Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17:548–558. 
  14. Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 2002;3:155–166. 
  15. Hemavathy K, Ashraf SI, Ip YT. Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene. 2000;257:1–12. 
  16. Grau Y, Carteret C, Simpson P. Mutations and chromosomal rearrangements affecting the expression of snail, a gene involved in embryonic patterning in DROSOPHILA MELANOGASTER. Genetics. 1984;108:347–360. [PMC free article] 
  17. Valdes F, Alvarez AM, Locascio A, Vega S, Herrera B, Fernandez M, Benito M, Nieto MA, Fabregat I. The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor Beta in fetal rat hepatocytes. Mol Cancer Res. 2002;1:68–78.
  18. Perez-Losada J, Sanchez-Martin M, Perez-Caro M, Perez-Mancera PA, Sanchez-Garcia I. The radioresistance biological function of the SCF/kit signaling pathway is mediated by the zinc-finger transcription factor Slug. Oncogene. 2003;22:4205–4211. 
  19. Vega S, Morales AV, Ocana OH, Valdes F, Fabregat I, Nieto MA. Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 2004;18:1131–1143. 
  20. Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol. 1993;5:806–811. 
  21. Wijnhoven BP, Dinjens WN, Pignatelli M. E-cadherin-catenin cell-cell adhesion complex and human cancer. Br J Surg. 2000;87:992–1005. doi: 10.1046/j.1365-2168.2000.01513.x. 
  22. Sakuragi N, Nishiya M, Ikeda K, Ohkouch T, Furth EE, Hareyama H, Satoh C, Fujimoto S. Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol. 1994;53:183–189. 
  23. Cheng L, Nagabhushan M, Pretlow TP, Amini SB, Pretlow TG. Expression of E-cadherin in primary and metastatic prostate cancer. Am J Pathol. 1996;148:1375–1380. [PMC free article] [PubMed[Google Scholar]
  24. Bremnes RM, Veve R, Gabrielson E, Hirsch FR, Baron A, Bemis L, Gemmill RM, Drabkin HA, Franklin WA. High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J Clin Oncol. 2002;20:2417–2428. 
  25. Graff JR, Herman JG, Lapidus RG, Chopra H, Xu R, Jarrard DF, Isaacs WB, Pitha PM, Davidson NE, Baylin SB. E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res. 1995;55:5195–5199. 
  26. Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hirohashi S. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci U S A. 1995;92:7416–7419. doi: 10.1073/pnas.92.16.7416. 
  27. Grooteclaes ML, Frisch SM. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene. 2000;19:3823–3828. doi: 10.1038/sj.onc.1203721.
  28. Comijn J, Berx G, Vermassen P, Verschueren K, Van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, Van Roy F. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001;7:1267–1278. doi: 10.1016/S1097-2765(01)00260-X. 
  29. Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, Nieto MA. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene. 2002;21:3241–3246. doi: 10.1038/sj.onc.1205416.
  30. Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, Van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 2003;63:2172–2178.
  31. Hajra KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res. 2002;62:1613–1618
  32. Sugimachi K, Tanaka S, Kameyama T, Taguchi K, Aishima S, Shimada M, Sugimachi K, Tsuneyoshi M. Transcriptional repressor snail and progression of human hepatocellular carcinoma. Clin Cancer Res. 2003;9:2657–2664. 
  33. Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000;2:84–89. doi: 10.1038/35000034.
  34. Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, Del Barrio MG, Portillo F, Nieto MA. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2:76–83. 
  35. Blechschmidt K, Sassen S, Schmalfeldt B, Schuster T, Hofler H, Becker KF. The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients. Br J Cancer. 2008;98:489–495. doi: 10.1038/sj.bjc.6604115. [PMC free article] [PubMed] [CrossRef[Google Scholar]
  36. Tuhkanen H, Soini Y, Kosma VM, Anttila M, Sironen R, Hamalainen K, Mannermaa A. Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression. BMC Cancer. 2009;9:289. doi: 10.1186/1471-2407-9-289. [PMC free article] 


Lascia un commento

Il tuo indirizzo email non sarà pubblicato. I campi obbligatori sono contrassegnati *

Captcha loading...