Cancer stem cells (CSCs) may be dedifferentiated somatic cells following oncogenic processes, representing a subpopulation of cells able to promote tumor growth with their capacities for proliferation and self-renewal, inducing lineage heterogeneity, which may be a main cause of resistance to therapies. It has been shown that the “less differentiated process” may have an impact on tumor plasticity, particularly when non-CSCs may dedifferentiate and become CSC-like. Bidirectional interconversion between CSCs and non-CSCs has been reported in other solid tumors, where the inflammatory stroma promotes cell reprogramming by enhancing Wnt signaling through nuclear factor kappa B activation in association with intracellular signaling, which may induce cells' pluripotency, the oncogenic transformation can be considered another important aspect in the acquisition of "new" development programs with oncogenic features. During cell reprogramming, mutations represent an initial step toward dedifferentiation, in which tumor cells switch from a partially or terminally differentiated stage to a less differentiated stage that is mainly manifested by re-entry into the cell cycle, acquisition of a stem cell-like phenotype, and expression of stem cell markers. This phenomenon typically shows up as a change in the form, function, and pattern of gene and protein expression, and more specifically, in CSCs. This review would highlight the main epigenetic alterations, major signaling pathways and driver mutations in which CSCs, in tumors and specifically, in lung cancer, could be involved, acting as key elements in the differentiation/dedifferentiation process. This would highlight the main molecular mechanisms which need to be considered for more tailored therapies.

中文翻译：

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肺癌干细胞在去分化过程驱动的表观遗传改变中的分子特征


癌症干细胞 （CSCs） 可能是经过致癌过程的去分化体细胞，代表能够促进肿瘤生长的细胞亚群，其增殖和自我更新能力，诱导谱系异质性，这可能是对治疗耐药的主要原因。已经表明，“分化程度较低的过程”可能对肿瘤可塑性产生影响，特别是当非 CSCs 可能去分化并变成 CSC 样时。在其他实体瘤中已经报道了 CSCs 和非 CSCs 之间的双向相互转换，其中炎症基质通过核因子 kappa B 激活增强 Wnt 信号传导来促进细胞重编程，这与细胞内信号传导相关，这可能诱导细胞的多能性，致癌转化可以被认为是获得具有致癌特征的“新”开发项目的另一个重要方面。在细胞重编程过程中，突变代表着去分化的初始步骤，其中肿瘤细胞从部分或终末分化阶段转变为分化程度较低的阶段，主要表现为重新进入细胞周期、获得干细胞样表型和干细胞标志物的表达。这种现象通常表现为基因和蛋白质表达的形式、功能和模式的变化，更具体地说，在 CSC 中。本文将重点介绍肿瘤中 CSCs（特别是肺癌中）可能参与的主要表观遗传改变、主要信号通路和驱动突变，它们是分化/去分化过程中的关键要素。这将突出需要考虑以进行更有针对性的治疗的主要分子机制。