Lamins regulate cancer cell plasticity and chemosensitivity
BackgroundStem cell plasticity plays key roles in mammalian organogenesis, tissue homeostasis, and carcinogenesis. Given its tolerance to anti-tumor therapy and its promotion on immunosuppressive microenvironment, cancer cell plasticity is a major contributor to cancer recurrence and metastasis. It...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1599175/full |
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| author | Guofang Chen Tingyi Wei Tingyi Wei Ao Huang Junwei Shen Furong Ju Shichao Huang Haisen Li Haisen Li |
| author_facet | Guofang Chen Tingyi Wei Tingyi Wei Ao Huang Junwei Shen Furong Ju Shichao Huang Haisen Li Haisen Li |
| author_sort | Guofang Chen |
| collection | DOAJ |
| description | BackgroundStem cell plasticity plays key roles in mammalian organogenesis, tissue homeostasis, and carcinogenesis. Given its tolerance to anti-tumor therapy and its promotion on immunosuppressive microenvironment, cancer cell plasticity is a major contributor to cancer recurrence and metastasis. It is necessary to explore novel avenues to resolve the limitations of current treatments.MethodsWe established stable cancer cell lines harboring all lamin knockdown and then explored the effects of all lamin deficiency on cancer plasticity and tumorigenesis in both cell and subcutaneous mouse models.ResultsWe found that all lamin knockdown disrupts cancer cell plasticity and impairs tumor progression. The deficiency of all lamin subtypes impaired the stemness and cell cycle transition of cancer cell. Lamin knockdown modulated genomic damage and repair pathways, inhibited mitochondrial function, and triggered cellular senescence. Moreover, lamin knockdown within cancer cell suppressed cancer growth in vivo by enhancing the infiltration and activation of functional T cells. Mechanistically, lamin knockdown reduced the expression of inhibitory immune checkpoints and inflammatory factors in cancer cell via the HIF-1 signaling pathway, which led to the increased sensitivity of cancer cells to chemotherapy.ConclusionsOverall, our findings characterize the significance of nuclear lamins in cancer cell plasticity and offer an attractive way to improve the effectiveness of anti-cancer therapy. |
| format | Article |
| id | doaj-art-26a3af4e22c941e3b553ee2ddea2aeaf |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-26a3af4e22c941e3b553ee2ddea2aeaf2025-08-20T03:33:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.15991751599175Lamins regulate cancer cell plasticity and chemosensitivityGuofang Chen0Tingyi Wei1Tingyi Wei2Ao Huang3Junwei Shen4Furong Ju5Shichao Huang6Haisen Li7Haisen Li8Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, ChinaNinth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, ChinaClinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, The Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, ChinaZhongshan Hospital, Fudan University, Shanghai, ChinaBackgroundStem cell plasticity plays key roles in mammalian organogenesis, tissue homeostasis, and carcinogenesis. Given its tolerance to anti-tumor therapy and its promotion on immunosuppressive microenvironment, cancer cell plasticity is a major contributor to cancer recurrence and metastasis. It is necessary to explore novel avenues to resolve the limitations of current treatments.MethodsWe established stable cancer cell lines harboring all lamin knockdown and then explored the effects of all lamin deficiency on cancer plasticity and tumorigenesis in both cell and subcutaneous mouse models.ResultsWe found that all lamin knockdown disrupts cancer cell plasticity and impairs tumor progression. The deficiency of all lamin subtypes impaired the stemness and cell cycle transition of cancer cell. Lamin knockdown modulated genomic damage and repair pathways, inhibited mitochondrial function, and triggered cellular senescence. Moreover, lamin knockdown within cancer cell suppressed cancer growth in vivo by enhancing the infiltration and activation of functional T cells. Mechanistically, lamin knockdown reduced the expression of inhibitory immune checkpoints and inflammatory factors in cancer cell via the HIF-1 signaling pathway, which led to the increased sensitivity of cancer cells to chemotherapy.ConclusionsOverall, our findings characterize the significance of nuclear lamins in cancer cell plasticity and offer an attractive way to improve the effectiveness of anti-cancer therapy.https://www.frontiersin.org/articles/10.3389/fonc.2025.1599175/fulllamincancer cell plasticityPD-L1chemosensitivityHIF-1 signaling |
| spellingShingle | Guofang Chen Tingyi Wei Tingyi Wei Ao Huang Junwei Shen Furong Ju Shichao Huang Haisen Li Haisen Li Lamins regulate cancer cell plasticity and chemosensitivity Frontiers in Oncology lamin cancer cell plasticity PD-L1 chemosensitivity HIF-1 signaling |
| title | Lamins regulate cancer cell plasticity and chemosensitivity |
| title_full | Lamins regulate cancer cell plasticity and chemosensitivity |
| title_fullStr | Lamins regulate cancer cell plasticity and chemosensitivity |
| title_full_unstemmed | Lamins regulate cancer cell plasticity and chemosensitivity |
| title_short | Lamins regulate cancer cell plasticity and chemosensitivity |
| title_sort | lamins regulate cancer cell plasticity and chemosensitivity |
| topic | lamin cancer cell plasticity PD-L1 chemosensitivity HIF-1 signaling |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1599175/full |
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