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Tumor reversion and embryo morphogenetic factors
Seminars in Cancer Biology ( IF 14.5 ) Pub Date : 2020-09-10 , DOI: 10.1016/j.semcancer.2020.09.005
Sara Proietti 1 , Alessandra Cucina 2 , Andrea Pensotti 3 , Andrea Fuso 4 , Cinzia Marchese 4 , Andrea Nicolini 5 , Mariano Bizzarri 4
Affiliation  

Several studies have shown that cancer cells can be “phenotypically reversed”, thus achieving a “tumor reversion”, by losing malignant hallmarks as migrating and invasive capabilities. These findings suggest that genome activity can switch to assume a different functional configuration, i.e. a different Gene Regulatory Network pattern. Indeed, once “destabilized”, cancer cells enter into a critical transition phase that can be adequately “oriented” by yet unidentified morphogenetic factors – acting on both cells and their microenvironment – that trigger an orchestrated array of structural and epigenetic changes. Such process can bypass genetic abnormalities, through rerouting cells toward a benign phenotype. Oocytes and embryonic tissues, obtained by animals and humans, display such “reprogramming” capability, as a number of yet scarcely identified embryo-derived factors can revert the malignant phenotype of several types of tumors. Mechanisms involved in the reversion process include the modification of cell-microenvironment cross talk (mostly through cytoskeleton reshaping), chromatin opening, demethylation, and epigenetic changes, modulation of biochemical pathways, comprising TCTP-p53, PI3K-AKT, FGF, Wnt, and TGF-β-dependent cascades.

Results herein discussed promise to open new perspectives not only in the comprehension of cancer biology but also toward different therapeutic options, as suggested by a few preliminary clinical studies.



中文翻译:

肿瘤逆转和胚胎形态发生因素

几项研究表明,癌细胞可以“表型逆转”,从而通过失去迁移和侵袭能力等恶性标志来实现“肿瘤逆转”。这些发现表明基因组活动可以转换为假设不同的功能配置不同的基因调控网络模式。事实上,一旦“不稳定”,癌细胞就会进入一个关键的过渡阶段,该阶段可以通过尚未确定的形态发生因素充分“定向”——作用于细胞及其微环境——这会触发一系列精心安排的结构和表观遗传变化。这样的过程可以绕过遗传异常,通过将细胞重新导向良性表型。动物和人类获得的卵母细胞和胚胎组织显示出这种“重编程”能力,因为许多尚未发现的胚胎衍生因子可以逆转几种肿瘤的恶性表型。参与逆转过程的机制包括细胞-微环境串扰的修改(主要通过细胞骨架重塑)、染色质开放、去甲基化和表观遗传变化,

正如一些初步临床研究所表明的,本文讨论的结果有望为癌症生物学的理解以及不同的治疗选择开辟新的视角。

更新日期:2020-09-10
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