Institute of Life Sciences, Chongqing Medical University, China.
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, China.
Mol Oncol. 2023 Dec;17(12):2743-2766. doi: 10.1002/1878-0261.13480. Epub 2023 Jul 1.
Although early diagnosis and therapeutic advances have transformed the living quality and outcome of cancer patients, the poor prognosis for metastatic patients has not been significantly improved. Mechanisms underlying the complexity of metastasis cannot be simply determined by the straightforward 'cause-and-effect relationships'. We have developed a 'dry-lab-driven knowledge discovery and wet-lab validation' approach to embrace the complexity of cancer and metastasis. We have revealed for the first time that polymetastatic (POL) melanoma cells can utilize both the secretory protein pathway (S100A11-Sec23a) and the exosomal crosstalk (miR-487a-5p) to transfer their 'polymetastatic competency' to the oligometastatic (OL) melanoma cells, via synergistic co-targeting of the tumor-suppressor Nudt21. The downstream deregulated glycolysis was verified to regulate metastatic colonization efficiency. Further, two gene sets conferring independent prognosis in melanoma were identified, which have the potential for clinical translation and merit future clinical validation.
尽管早期诊断和治疗进展已经改变了癌症患者的生活质量和预后，但转移性患者的预后仍未得到显著改善。转移的复杂性机制不能简单地通过直接的“因果关系”来确定。我们开发了一种“干实验驱动的知识发现和湿实验验证”方法来应对癌症和转移的复杂性。我们首次揭示了多转移（POL）黑色素瘤细胞可以利用分泌蛋白途径（S100A11-Sec23a）和外泌体串扰（miR-487a-5p），通过协同靶向肿瘤抑制因子 Nudt21，将其“多转移能力”转移到寡转移（OL）黑色素瘤细胞中。下游失调的糖酵解被证实可调节转移定植效率。此外，还鉴定了两个在黑色素瘤中具有独立预后作用的基因集，它们具有临床转化的潜力，值得未来的临床验证。
