Normal Gelişim Süreci ve Karsinogenezde Epitel-Mezenkimal Dönüşüm

Epitel-mezenkimal değişim EMD , bir çok morfolojik ve biyokimyasal değişiklikler sonucu epitel hücrelerinin epitel özelliklerini kaybederek mezenkimal özellikler kazanmalarına sebep olan önemli bir gelişim sürecidir. EMD'nin sonucunda kompakt ve düzenli olan epitel hücreleri normal gelişim sürecinde organizmanın farklı kısımlarına göç ederek bu kısımlarda farklı dokuları oluşturabilmelerini olanaklı kılan daha az kompakt ve hareketli bir yapı kazanırlar. Birincil tümörlerin EMD geçiren epitel hücreleri istilaci ve göç edici özellikler kazandığından, EMD karsinogenez sırasındaki metastaz oluşumuna da katkı sağlamış olur. Patolojik ve normal EMD arasındaki moleküler ve hücresel benzerlikler nedeniyle, normal gelişim sırasında gerçekleşen EMD sürecini ve regülasyonu anlamak karsinogenezi daha iyi anlamamızı sağlayabilir.

Anahtar Kelimeler:

epitel-mezenkimal değişim, TGF-ß, karsinogenez, embrionik gelişim

Epithelial-Mesenchymal Transition in Normal Development and Carcinogenesis

Epithelial-mesenchymal transition EMT is an important developmental process allowing epithelial cells to loose their epithelial properties and gain mesenchymal characteristics through a series of morphological and biochemical changes. As a result of EMT, compact and ordered epithelial cells become less compact and motile, enabling them to migrate to different sites and generate different tissues during normal development. EMT also contributes to metastasis during carcinogenesis, as the epithelial cells of primary tumors undergoing EMT become invasive and migratory. Understanding the EMT process and its regulation during embryonic development may advance our knowledge on carcinogenesis based on the molecular and cellular similarities between pathological and developmental EMT.

Keywords:

Epithelial-mesenchymal transition, TGF-ß, carcinogenesis, embryonic development,

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Acloque H, Adams MS, Fishwick K, Bronner-Fra- ser M, Nieto MA. Epithelial-mesenchymal tran- sitions: the importance of changing cell state in development and disease. J Clin Invest.,2009; 119: 1438–1449.
Boyer, B., Valles, A.M., Edme, N. Induction and re- gulation of epithelial-mesenchymal transitions. Biochem. Pharmacol., 2000;60:1091-1099.
Casas E, Kim J, Bendesky A, Ohno-Machado L, Wolfe CJ, Yang J. Snail2 is an Essential Mediator of Twist1-Induced Epithelial Mesenchymal Tran- sition and Metastasis. Cancer Res., 2011;71:245- 254.
Fuxe J, Karlsson MC. TGF- ß -induced epitheli- al-mesenchymal transition: A link between can- cer and inflammation. Semin Cancer Biol., 2012; 22:455-461.
Heldin CH, Vanlandewijck M, Moustakas A. Regu- lation of EMT by TGFb in cancer. FEBS Lett., 2012; 586:1959-1970.
Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest., 2009; 119:1417-1419.
Kalluri R, Weinberg RAThe basics of epitheli- al-mesenchymal transition. J Clin Invest.,2009; 119:1420-1428.
Kang Y, Massagué J. Epithelial-Mesenchymal Transitions: Twist in Development and Metasta- sis. Cell, 2004; 118: 277-279.
Lee K, Nelson CM. New Insights into the Regu- lation of Epithelial–Mesenchymal Transition and Tissue Fibrosis. Int Rev Cell Mol Biol., 2012; 294:171-221.
Micalizzi DS, Farabaugh SM, Ford HL. Epitheli- al-mesenchymal transition in cancer: parallels between normal development and tumor prog- ression. J. Mammary Gland Biol Neoplasia., 2010; 15:117-134.
Nieto, M.A. The snail superfamily of zinc-finger transcription factors. Nat. Rev. Mol. Cell Biol., 2002; 3:155-166.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Scien- ce, 1999;143-147.
Popov Z., Gil-Diez de Medina S., Lefrere-Bel- da MA., Hoznek A., Bastuji-Garin S., Abbou CC, Thiery JP., Radvanyi F., Chopin DKLow E-cadherin expression in bladder cancer at the transcriptio- nal and protein level provides prognostic infor- mation. Br J Cancer., 2000; 83: 209–214.
Radisky DC. Epithelial-mesenchymal transition. J Cell Sci., 2005; 118 :4325-4326.
sai, R.Y., Kittappa, R., McKay, R.D. Plasticity, nic- hes, and the use of stem cells. Dev. Cell., 2002; 2:707-712.
Veerle L., Van Marck, E. Bracke. (2000). Epithe- lial-mesencymal transition in human cancer. Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; -. Available from: hhtp://www.ncbi.nih.gov/books/NBK5974/
Wu CY, Tsai YP, Wu MZ, Teng SC, Wu KJ. Epige- netic reprogramming and post- transcriptional regulation during the epithelial–mesenchymal transition. Trends Genet., 2012; 28:454-463.
Zhao XJ., Li H., Chen H., Liu YX.,Zhang LH., Liu SX., Feng QL. Expression of e-cadherin and be- ta-catenin in human esophageal squamous cell carcinoma: relationships with prognosis. World J Gastroenterol., 2003; 9:225-232.