Xu Jiali, Zhang Houde, Nie Zhihao, He Wenyou, Zhao Yichao, Huang Zhenhui, Jia Lin, Du Zhiye, Zhang Baotong, Xia Siyuan
Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.
Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Neoplasia. 2025 Mar;61:101134. doi: 10.1016/j.neo.2025.101134. Epub 2025 Feb 6.
Cell plasticity emerges as a novel cancer hallmark and is pivotal in driving tumor heterogeneity and adaptive resistance to different therapies. Cancer stem-like cells (CSCs) are considered the root of cancer. While first defined as tumor-initiating cells with the potential to develop a heterogeneous tumor, CSCs further demonstrate their roles in cancer metastasis and adaptive therapeutic resistance. Generally, CSCs come from the malignant transformation of somatic stem cells or the de-differentiation of other cancer cells. The resultant cells gain more plasticity and are ready to differentiate into different cell states, enabling them to adapt to therapies and metastatic ecosystems. Therefore, CSCs are likely the nature of tumor cells that gain cell plasticity. However, the phenotypic plasticity of CSCs has never been systematically discussed. Here, we review the distinct intrinsic signaling pathways and unique microenvironmental niches that endow CSC plasticity in solid tumors to adapt to stressful conditions, as well as emerging opportunities for CSC-targeted therapy.
细胞可塑性作为一种新的癌症标志出现，在驱动肿瘤异质性和对不同疗法的适应性耐药中起关键作用。癌症干细胞（CSCs）被认为是癌症的根源。虽然最初被定义为具有发展异质性肿瘤潜力的肿瘤起始细胞，但CSCs进一步证明了它们在癌症转移和适应性治疗耐药中的作用。一般来说，CSCs来自体细胞干细胞的恶性转化或其他癌细胞的去分化。产生的细胞获得了更大的可塑性，并准备好分化成不同的细胞状态，使它们能够适应治疗和转移生态系统。因此，CSCs可能是获得细胞可塑性的肿瘤细胞的本质。然而，CSCs的表型可塑性从未被系统地讨论过。在这里，我们综述了赋予实体瘤中CSC可塑性以适应应激条件的独特内在信号通路和独特微环境龛，以及CSC靶向治疗的新机遇。
