The heterogeneity of cancer stem-like cells at the invasive front.
The heterogeneity of cancer stem-like cells at the invasive front.
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DOI：
10.1186/s12935-017-0393-y
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发表时间：
2017
影响因子：
5.8
通讯作者：
Yoshida GJ
中科院分区：
文献类型：
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作者：
Yoshida GJ
肿瘤干细胞在常规抗癌治疗后，能在最小残留病变下存活并长期存在，具有多种功能。实体恶性肿瘤的癌干细胞样细胞高度表达CD44v8-10（由选择性剪接产生的CD44的变体异构体），通过ESRP1-CD44v-xCT（胱氨酸/谷氨酸反转运体）轴介导的谷胱甘肽的强大产生，具有抗氧化还原应激的能力。据报道，CD44v和c-Myc在侵袭性肿瘤的侵袭前倾向于表现出相反的表达模式。考虑到活性氧的积累触发了Wnt/β-catenin信号通路的激活，我们假设CD44v通过减弱ros诱导的Wnt信号通路调控c-Myc表达的负反馈机制。为了解决增殖性和静止性癌症干细胞样细胞是否以及如何异质性地存在于侵袭/转移边缘的基本问题，研究人员需要研究c-Myc降解所必需的e3 -泛素连接酶活性。CSCs在侵袭/转移前沿的异质性有望证明肿瘤在抗癌治疗的选择压力下的动态演变。此外，将建立新的分子靶向治疗策略，结合典型的药物重定位与xCT抑制剂，破坏异质CSC群体中精细调节的c-Myc表达。
Cancer stem-like cells exhibit the multi-functional roles to survive and persist for a long period in the minimal residual disease after the conventional anti-cancer treatments. Cancer stem-like cells of solid malignant tumors which highly express CD44v8-10, the variant isoform of CD44 generated by alternative splicing, has a resistance to redox stress by the robust production of glutathione mediated by ESRP1-CD44v-xCT (cystine/glutamate antiporter) axis. It has been reported that CD44v and c-Myc tend to show the inversed expression pattern at the invasive front of the aggressive tumors. Given that the accumulation of reactive oxygen species triggers the activation of Wnt/β-catenin signal pathway, it is hypothesized that CD44v causes the negative feedback machinery in the regulation of c-Myc expression via the attenuated ROS-induced Wnt signal pathway. To address the fundamental question whether and how both proliferative and quiescent cancer stem-like cells heterogeneously exist at the invasive/metastatic edge, researchers need to investigate into the E3-ubiquitin ligase activity essential for c-Myc degradation. CSCs heterogeneity at the invasive/metastatic front is expected to demonstrate the dynamic tumor evolution with the selective pressure of anti-cancer treatments. Furthermore, the novel molecular targeting therapeutic strategies would be established to disrupt the finely-regulated c-Myc expression in the heterogeneous CSC population in combination with the typical drug-repositioning with xCT inhibitor.