MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells

作者：Minying Zheng, Shifeng Tian, Xinyue Zhou, Man Yan, Ming‐Ming Zhou, Yongjun Yu, Yue Zhang, Xiaorui Wang, Na Li, Li Ren, Shiwu Zhang · 发表于：Oncology Reports · 年份：2024 · DOI：10.3892/or.2024.8722 · 被引用次数：10 · 研究领域：Cancer, Hypoxia, and Metabolism、Epigenetics and DNA Methylation、Cancer-related Molecular Pathways

High concentrations of cobalt chloride (CoCl 2 ) can induce the formation of polyploid giant cancer cells (PGCCs) in various tumors, which can produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric division. To study the role of hypoxia‑inducible factor (HIF) 1α in the formation of PGCCs, colon cancer cell lines Hct116 and LoVo were used as experimental subjects. Western blotting, nuclear and cytoplasmic protein extraction and immunocytochemical experiments were used to compare the changes in the expression and subcellular localization of HIF1α, microphthalmia‑associated transcription factor (MITF), protein inhibitor of activated STAT protein 4 (PIAS4) and von Hippel‑Lindau disease tumor suppressor (VHL) after treatment with CoCl 2 . The SUMOylation of HIFα was verified by co‑immunoprecipitation assay. After inhibiting HIF1α SUMOylation, the changes in proliferation, migration and invasion abilities of Hct116 and LoVo were compared by plate colony formation, wound healing and Transwell migration and invasion. In addition, lysine sites that led to SUMOylation of HIF1α were identified through site mutation experiments. The results showed that CoCl 2 can induce the formation of PGCCs with the expression level of HIF1α higher in treated cells than in control cells. HIF1α was primarily located in the cytoplasm of control cell. Following CoCl 2 treatment, the subcellular localization of HIF1α was primarily in the nuclei of PGCCs with dau...