DiNatale Anthony, Castelli Maria Sofia, Nash Bradley, Meucci Olimpia, Fatatis Alessandro
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Present Address: Janssen Oncology, Spring House, PA, USA.
J Cancer. 2022 Aug 27;13(11):3160-3176. doi: 10.7150/jca.72331. eCollection 2022.
Tumor-initiating cells (TICs) are a rare sub-population of cells within the bulk of a tumor that are major contributors to tumor initiation, metastasis, and chemoresistance. TICs have a stem-cell-like phenotype that is dictated by the expression of master regulator transcription factors, including OCT4, NANOG, and SOX2. These transcription factors are expressed via activation of multiple signaling pathways that drive cancer initiation and progression. Importantly, these same signaling pathways can be activated by select chemokine receptors. Chemokine receptors are increasingly being revealed as major drivers of the TIC phenotype, as their signaling can lead to activation of stemness-controlling transcription factors. Additionally, the cell surface expression of chemokine receptors provides a unique therapeutic target to disrupt signaling pathways that control the expression of master regulator transcription factors and the TIC phenotype. This review summarizes the master regulator transcription factors known to dictate the TIC phenotype, along with the complex signaling pathways that can mediate their expression and the chemokine receptors that are most upstream of this phenotype.
肿瘤起始细胞（TICs）是肿瘤主体内的一种罕见细胞亚群，对肿瘤的起始、转移和化疗耐药起主要作用。TICs具有类似干细胞的表型，这由包括OCT4、NANOG和SOX2在内的主调控转录因子的表达所决定。这些转录因子通过驱动癌症起始和进展的多种信号通路的激活而表达。重要的是，这些相同的信号通路可被特定的趋化因子受体激活。趋化因子受体越来越多地被揭示为TIC表型的主要驱动因素，因为它们的信号传导可导致干性控制转录因子的激活。此外，趋化因子受体的细胞表面表达提供了一个独特的治疗靶点，以破坏控制主调控转录因子表达和TIC表型的信号通路。本综述总结了已知决定TIC表型的主调控转录因子，以及可介导其表达的复杂信号通路和该表型最上游的趋化因子受体。
