Tumorigenesis is associated with the development of a highly variable pattern of cellular diversity, consequence of genetic and epigenetic diversification, followed by clonal selection and expansion. This process is shaped by the microenvironment and leads to intratumoral heterogeneity, which is characterized by differences between cancer cells in terms of gene expression, phenotypic markers, growth dynamics, and resistance to treatment. Another relevant aspect in intratumor heterogeneity is cell plasticity—the ability of a cell to switch to new identities. In this review, we focus on the mechanisms that regulate cancer cell plasticity within a tumor, and explore the concept of tumor propagating cells, or TPCs, a cancer cell able to propagate/phenocopy the parental tumor and recapitulate tumor heterogeneity. We discuss the influence of the microenvironment and driver mutations on TPCs formation and function, the existence of phenotypically distinct TPC clones within a tumor, the evolution of TPCs with disease progression, and their implications for therapy.

肿瘤发生与细胞多样性的高度可变模式的发展有关，这是遗传和表观遗传多样化的结果，随后是克隆选择和扩增。这一过程受微环境影响并导致肿瘤内异质性，其特点是癌细胞在基因表达、表型标志物、生长动力学和治疗耐药性方面存在差异。肿瘤内异质性的另一个相关方面是细胞可塑性——细胞转换为新身份的能力。在这篇综述中，我们专注于调节肿瘤内癌细胞可塑性的机制，并探索肿瘤增殖细胞（TPCs）的概念，一种能够增殖/表型复制亲本肿瘤并概括肿瘤异质性的癌细胞。