Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer.

Leonardo Marques da Fonseca, Israel Diniz-Lima, Marcos André Rodrigues da Costa Santos, Tatiany Nunes Franklim, Kelli Monteiro da Costa, Ariely Costa Dos Santos, Alexandre Morrot, Debora Decote-Ricardo, Raphael do Carmo Valente, Celio Geraldo Freire-de-Lima, Jhenifer Santos Dos Reis, Leonardo Freire-de-Lima
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Abstract

Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis.

Abstract Image

Abstract Image

苦乐参半的糖:不同寻常的聚糖结构如何连接癌症的上皮到间质转化和多药耐药。
癌细胞的特点是代谢重编程,这使它们能够在通常不适宜生存的条件下存活。近年来,有一个非常充分的例子引起了人们的注意,并且已经被认为是转化细胞的一个标志,那就是碳水化合物代谢的重编程。这种特征与参与糖缀合物生物合成的酶(通常称为糖基转移酶)的差异表达有关,与健康组织中的表达相比,导致结构不典型聚糖的表达。最新的研究表明,糖表型改变能够调节对疾病的发生和/或进展至关重要的多因素事件。在本文中,我们将讨论糖生物学在现代医学中的重要性,重点关注异常/截断的o链聚糖调节癌症进展中两个复杂而必要的现象的能力:多药耐药(MDR)表型的获得和与上皮-间质转化(EMT)过程相关的分子途径的激活,这一过程与癌症转移密切相关。
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