Pádua Diana, Figueira Paula, Ribeiro Inês, Almeida Raquel, Mesquita Patrícia
i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
Front Cell Dev Biol. 2020 Jun 18;8:442. doi: 10.3389/fcell.2020.00442. eCollection 2020.
Gastric and colorectal cancers have a high incidence and mortality worldwide. The presence of cancer stem cells (CSCs) within the tumor mass has been indicated as the main reason for tumor relapse, metastasis and therapy resistance, leading to poor overall survival. Thus, the elimination of CSCs became a crucial goal for cancer treatment. The identification of these cells has been performed by using cell-surface markers, a reliable approach, however it lacks specificity and usually differs among tumor type and in some cases even within the same type. In theory, the ideal CSC markers are those that are required to maintain their stemness features. The knowledge that CSCs exhibit characteristics comparable to normal stem cells that could be associated with the expression of similar transcription factors (TFs) including SOX2, OCT4, NANOG, KLF4 and c-Myc, and signaling pathways such as the Wnt/-catenin, Hedgehog (Hh), Notch and PI3K/AKT/mTOR directed the attention to the use of these similarities to identify and target CSCs in different tumor types. Several studies have demonstrated that the abnormal expression of some TFs and the dysregulation of signaling pathways are associated with tumorigenesis and CSC phenotype. The disclosure of common and appropriate biomarkers for CSCs will provide an incredible tool for cancer prognosis and treatment. Therefore, this review aims to gather the new insights in gastric and colorectal CSC identification specially by using TFs as biomarkers and divulge promising drugs that have been found and tested for targeting these cells.
胃癌和结直肠癌在全球范围内具有较高的发病率和死亡率。肿瘤块内癌症干细胞（CSCs）的存在被认为是肿瘤复发、转移和治疗耐药的主要原因，导致总体生存率较低。因此，消除CSCs成为癌症治疗的关键目标。通过使用细胞表面标志物来识别这些细胞，这是一种可靠的方法，然而它缺乏特异性，并且通常在肿瘤类型之间存在差异，在某些情况下甚至在同一类型内也有所不同。理论上，理想的CSC标志物是那些维持其干性特征所必需的标志物。已知CSCs表现出与正常干细胞相似的特征，这可能与包括SOX2、OCT4、NANOG、KLF4和c-Myc在内的相似转录因子（TFs）的表达以及Wnt/β-连环蛋白、Hedgehog（Hh）、Notch和PI3K/AKT/mTOR等信号通路有关，这使得人们将注意力转向利用这些相似性来识别和靶向不同肿瘤类型中的CSCs。多项研究表明，一些TFs的异常表达和信号通路的失调与肿瘤发生和CSC表型有关。揭示CSCs常见且合适的生物标志物将为癌症预后和治疗提供一个极好的工具。因此，本综述旨在收集特别是利用TFs作为生物标志物在胃癌和结直肠癌CSC识别方面的新见解，并公布已发现和测试的针对这些细胞的有前景的药物。
