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

  • Authors:
    • Minying Zheng
    • Shifeng Tian
    • Xinyue Zhou
    • Man Yan
    • Mingming Zhou
    • Yongjun Yu
    • Yue Zhang
    • Xiaorui Wang
    • Na Li
    • Li Ren
    • Shiwu Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Tianjin Union Medical Center, Tianjin 300121, P.R. China, Graduate School, Tianjin Medical University, Tianjin 300070, P.R. China, Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China, Department of Clinical Laboratory, Tianjin Medical University Cancer Institution and Hospital, Tianjin 300090, P.R. China
    Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 63
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    Published online on: March 6, 2024
       https://doi.org/10.3892/or.2024.8722
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Abstract

High concentrations of cobalt chloride (CoCl2) 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 CoCl2. 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 CoCl2 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 CoCl2 treatment, the subcellular localization of HIF1α was primarily in the nuclei of PGCCs with daughter cells (PDCs). After treatment with SUMOylation inhibitors, the nuclear HIF1α expression in PDCs decreased. Furthermore, their proliferation, migration and invasion abilities also decreased. After inhibiting the expression of MITF, the expression of HIF1α decreased. MITF can regulate HIF1α SUMOylation. Expression and subcellular localization of VHL and HIF1α did not change following PIAS4 knockdown. SUMOylation of HIF1α occurs at the amino acid sites K391 and K477 in PDCs. After mutation of the two sites, nuclear expression of HIF1α in PDCs was reduced, along with a significant reduction in the proliferation, migration and invasion abilities. In conclusion, the post‑translation modification regulated the subcellular location of HIF1α and the nuclear expression of HIF1α promoted the proliferation, migration and invasion abilities of PDCs. MITF could regulate the transcription and protein levels of HIF1α and participate in the regulation of HIF1α SUMOylation.
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Copy and paste a formatted citation
Spandidos Publications style
Zheng M, Tian S, Zhou X, Yan M, Zhou M, Yu Y, Zhang Y, Wang X, Li N, Ren L, Ren L, et al: MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells. Oncol Rep 51: 63, 2024.
APA
Zheng, M., Tian, S., Zhou, X., Yan, M., Zhou, M., Yu, Y. ... Zhang, S. (2024). MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells. Oncology Reports, 51, 63. https://doi.org/10.3892/or.2024.8722
MLA
Zheng, M., Tian, S., Zhou, X., Yan, M., Zhou, M., Yu, Y., Zhang, Y., Wang, X., Li, N., Ren, L., Zhang, S."MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells". Oncology Reports 51.5 (2024): 63.
Chicago
Zheng, M., Tian, S., Zhou, X., Yan, M., Zhou, M., Yu, Y., Zhang, Y., Wang, X., Li, N., Ren, L., Zhang, S."MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells". Oncology Reports 51, no. 5 (2024): 63. https://doi.org/10.3892/or.2024.8722
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng M, Tian S, Zhou X, Yan M, Zhou M, Yu Y, Zhang Y, Wang X, Li N, Ren L, Ren L, et al: MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells. Oncol Rep 51: 63, 2024.
APA
Zheng, M., Tian, S., Zhou, X., Yan, M., Zhou, M., Yu, Y. ... Zhang, S. (2024). MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells. Oncology Reports, 51, 63. https://doi.org/10.3892/or.2024.8722
MLA
Zheng, M., Tian, S., Zhou, X., Yan, M., Zhou, M., Yu, Y., Zhang, Y., Wang, X., Li, N., Ren, L., Zhang, S."MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells". Oncology Reports 51.5 (2024): 63.
Chicago
Zheng, M., Tian, S., Zhou, X., Yan, M., Zhou, M., Yu, Y., Zhang, Y., Wang, X., Li, N., Ren, L., Zhang, S."MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells". Oncology Reports 51, no. 5 (2024): 63. https://doi.org/10.3892/or.2024.8722
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