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Hypoxia-Induced Active Dynamics Promotes Early Tumorigenesis

Wang, Z.; Tian, L.; Li, B.

2025-01-02 cancer biology
10.1101/2024.12.31.630973 bioRxiv
Show abstract

Understanding early tumor formation is essential for cancer prevention, but most studies focus on later stages. Hypoxia, a key feature of the tumor microenvironment, influences cancer progression, yet its impact on early tumorigenesis remains vague. Here, we record 3D tumor spheroid development under hypoxic conditions by live cell imaging, enabling the first real-time study of tumor formation from a single cell. We find that hypoxia accelerates tumorigenesis by promoting directional movement and spheroid fusion. Meanwhile, hypoxia induces genetic instability, indicated by tiny nuclei cells and chromosomal aneuploidy. The interplay between dynamic and genetic instability optimizes the mechanical properties of the spheroid, creating positive feedback that drives further proliferation. These findings suggest potential strategies for early cancer prevention by targeting the environmental factors that influence dynamic-genetic coupling.

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