The reconstitution of the tumorigenesis process would shed light on the tumor development study and further drug selection strategies. To construct a tumorigenesis model and explore potential mechanism is of great importance. In our study, we observed that CDC20-knockdown cells cultured in acidic environment exhibited chromosomal instability and better survival ability. The tumorigenic metabolism transformation was confirmed through the increase of the extracellular acidification rate (ECAR) and decrease of the oxygen consumption rate (OCR) in CDC20-knockdown cells. After a long-term culture for 3–4 months, CDC20-knockdown cells in acidic medium showed a strong tumor formation ability by subcutaneous injection into mice that is similar to that of tumor cells. Meanwhile, transcriptome analysis of cells from different stages showed that stage D cells almost resembled the phenotype of immortal cancer cells. The oncogene accumulation laid a firm foundation in the development of the tumorigenesis process by suppressing autophagy and p53-induced apoptosis. Several autophage- and apoptosis-related genes showed inhibition during this tumorigenesis process. In summary, chromosomal instability induced by CDC20 knockdown and acidic microenvironment could collaboratively promote cell tumorigenesis through the downregulation of autophagy and apoptosis.

肿瘤发生过程的重建将为肿瘤发展研究和进一步的药物选择策略提供启示。建立肿瘤发生模型并探讨其潜在机制具有重要意义。在我们的研究中，我们观察到在酸性环境中培养的CDC20基因敲低细胞表现出染色体不稳定和更好的存活能力。通过降低CDC20击倒细胞的细胞外酸化率（ECAR）和降低耗氧率（OCR）证实了致瘤代谢转化。经过长期培养3-4个月后，在酸性培养基中CDC20-knockdown细胞通过与小鼠皮下注射类似的肿瘤细胞表现出强大的肿瘤形成能力。与此同时，不同阶段细胞的转录组分析表明，D期细胞几乎类似于永生癌细胞的表型。癌基因的积累通过抑制自噬和p53诱导的细胞凋亡为肿瘤发生过程的发展奠定了坚实的基础。在此肿瘤发生过程中，一些自噬和凋亡相关基因显示出抑制作用。总之，由CDC20敲低和酸性微环境引起的染色体不稳定性可以通过下调自噬和凋亡来共同促进细胞肿瘤发生。在此肿瘤发生过程中，一些自噬和凋亡相关基因显示出抑制作用。总之，由CDC20敲低和酸性微环境引起的染色体不稳定性可以通过下调自噬和凋亡来共同促进细胞肿瘤发生。在此肿瘤发生过程中，一些自噬和凋亡相关基因显示出抑制作用。总之，由CDC20敲低和酸性微环境引起的染色体不稳定性可以通过下调自噬和凋亡来共同促进细胞肿瘤发生。