Tsintarakis Antonis, Papalouka Chara, Kontarini Christina, Zoumpourlis Panagiotis, Karakostis Konstantinos, Adamaki Maria, Zoumpourlis Vassilis
Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece.
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
Life (Basel). 2023 Jun 9;13(6):1361. doi: 10.3390/life13061361.
Complex signaling interactions between cancer cells and their microenvironments drive the clonal selection of cancer cells. Opposing forces of antitumor and tumorigenic potential regulate the survival of the fittest clones, while key genetic and epigenetic alterations in healthy cells force them to transform, overcome cell senescence, and proliferate in an uncontrolled manner. Both clinical samples and cancer cell lines provide researchers with an insight into the complex structure and hierarchy of cancer. Intratumor heterogeneity allows for multiple cancer cell subpopulations to simultaneously coexist within tumors. One category of these cancer cell subpopulations is cancer stem cells (CSCs), which possess stem-like characteristics and are not easily detectable. In the case of breast cancer, which is the most prevalent cancer type among females, such subpopulations of cells have been isolated and characterized via specific stem cell markers. These stem-like cells, known as breast cancer stem cells (BCSCs), have been linked to major events during tumorigenesis including invasion, metastasis and patient relapse following conventional therapies. Complex signaling circuitries seem to regulate the stemness and phenotypic plasticity of BCSCs along with their differentiation, evasion of immunosurveillance, invasiveness and metastatic potential. Within these complex circuitries, new key players begin to arise, with one of them being a category of small non-coding RNAs, known as miRNAs. Here, we review the importance of oncogenic miRNAs in the regulation of CSCs during breast cancer formation, promotion and metastasis, in order to highlight their anticipated usage as diagnostic and prognostic tools in the context of patient stratification and precision medicine.
癌细胞与其微环境之间复杂的信号相互作用驱动了癌细胞的克隆选择。抗肿瘤和致瘤潜力的相反力量调节着最适应克隆的存活，而健康细胞中的关键基因和表观遗传改变迫使它们发生转化、克服细胞衰老并以不受控制的方式增殖。临床样本和癌细胞系都为研究人员提供了对癌症复杂结构和层次的深入了解。肿瘤内异质性使得多个癌细胞亚群能够在肿瘤中同时共存。这些癌细胞亚群中的一类是癌症干细胞（CSCs），它们具有干细胞样特征且不易被检测到。在女性中最常见的癌症类型乳腺癌中，这类细胞亚群已通过特定的干细胞标志物被分离和鉴定。这些被称为乳腺癌干细胞（BCSCs）的干细胞样细胞与肿瘤发生过程中的重大事件有关，包括侵袭、转移以及传统治疗后患者的复发。复杂的信号通路似乎调节着BCSCs的干性和表型可塑性以及它们的分化、免疫监视逃避、侵袭性和转移潜力。在这些复杂的通路中，新的关键参与者开始出现，其中之一是一类被称为miRNAs的小非编码RNA。在这里，我们综述致癌性miRNAs在乳腺癌形成、进展和转移过程中对CSCs调节的重要性，以便突出它们在患者分层和精准医学背景下作为诊断和预后工具的预期用途。
