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CDK1 promotes the stemness of lung cancer cells through interacting with Sox2

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Abstract

Objectives

The promoting roles of cyclin dependent kinase 1 (CDK1) have been revealed in various tumors, however, its effects in the progression of cancer stem cells are still confusing. This work aims to explore the roles of CDK1 in regulating the stemness of lung cancer cells.

Methods

Online dataset analysis was performed to evaluate the correlation between CDK1 exression and the survival of lung cancer patients. RT-qPCR, western blot, cell viability, sphere-formation analysis and ALDH activity detection were used to investigate the roles of CDK1 on lung cancer cell stemness, viability and chemotherapeutic sensitivity. Immunocoprecipitation (Co-IP) analysis and rescuing experiments were performed to reveal the underlying mechanisms contributing to CDK1-mediated effects on lung cancer cell stemness.

Results

CDK1 mRNA expression was negatively correlated with the overall survival of lung cancer patients and remarkably increased in tumor spheres formed by lung cancer cells compared to the parental cells. Additionally, CDK1 positively regulated the stemness of lung cancer cells. Mechanistically, CDK1 could interact with Sox2 protein, but not other stemness markers (Oct4, Nanog and CD133). Furthermore, CDK1 increased the phosphorylation, cytoplasm-nuclear translocation and transcriptional activity of Sox2 protein in lung cancer cells. Moreover, CDK1 positively regulated the stemness of lung cancer cells in a Sox2-dependent manner. Finally, we revealed that inhibition of CDK1 enhanced the chemotherapeutic sensitivity, which was also rescued by Sox2 overexpression.

Conclusions

This work reveals a novel CDK1/Sox2 axis responsible for maintaining the stemness of lung cancer cells.

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References

  1. Eide CA, Druker BJ. Understanding cancer from the stem cells up. Nat Med. 2017;23(6):656–7.

    Article  CAS  Google Scholar 

  2. Clarke MF. Clinical and therapeutic implications of cancer stem cells. N Engl J Med. 2019;380(23):2237–45.

    Article  CAS  Google Scholar 

  3. Buczacki SJA, Popova S, Biggs E, et al. Itraconazole targets cell cycle heterogeneity in colorectal cancer. J Exp Med. 2018;215(7):1891–912.

    Article  CAS  Google Scholar 

  4. Zhong L, Hu MM, Bian LJ, Liu Y, Chen Q, Shu HB. Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in mitosis. Cell Discov. 2020;6:26.

    Article  CAS  Google Scholar 

  5. Neganova I, Tilgner K, Buskin A, et al. CDK1 plays an important role in the maintenance of pluripotency and genomic stability in human pluripotent stem cells. Cell Death Dis. 2014;5:e1508.

    Article  CAS  Google Scholar 

  6. Heo J, Noh BJ, Lee S, et al. Phosphorylation of TFCP2L1 by CDK1 is required for stem cell pluripotency and bladder carcinogenesis. EMBO Mol Med. 2020;12(1):e10880.

    Article  CAS  Google Scholar 

  7. Zhang WW, Zhang XJ, Liu HX, et al. Cdk1 is required for the self-renewal of mouse embryonic stem cells. J Cell Biochem. 2011;112(3):942–8.

    Article  CAS  Google Scholar 

  8. Ravindran Menon D, Luo Y, Arcaroli JJ, et al. CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma. Cancer Res. 2018;78(23):6561–74.

    Article  Google Scholar 

  9. Menon DR, Fujita M. A state of stochastic cancer stemness through the CDK1-SOX2 axis. Oncotarget. 2019;10(27):2583–5.

    Article  Google Scholar 

  10. Zheng YB, Gong JH, Liu XJ, Li Y, Zhen YS. A CD13-targeting peptide integrated protein inhibits human liver cancer growth by killing cancer stem cells and suppressing angiogenesis. Mol Carcinog. 2017;56(5):1395–404.

    Article  CAS  Google Scholar 

  11. Gao L, Sang JZ, Cao H. Limonin enhances the radiosensitivity of nasopharyngeal carcinoma cells via attenuating Stat3-induced cell stemness. Biomed Pharmacother. 2019;118:109366.

    Article  CAS  Google Scholar 

  12. Tang Q, Chen Z, Zhao L, Xu H. Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1. Aging (Albany NY). 2019;11(22):9982–99.

    Article  CAS  Google Scholar 

  13. Li M, He F, Zhang Z, Xiang Z, Hu D. CDK1 serves as a potential prognostic biomarker and target for lung cancer. J Int Med Res. 2020;48(2):300060519897508.

    CAS  PubMed  Google Scholar 

  14. Gyorffy B, Surowiak P, Budczies J, Lanczky A. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS ONE. 2013;8(12):e82241.

    Article  Google Scholar 

  15. Zheng L, Li X, Gu Y, Lv X, Xi T. The 3’UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1. Breast Cancer Res Treat. 2015;150(1):105–18.

    Article  CAS  Google Scholar 

  16. Qian S, Wang W, Li M. Transcriptional factor Yin Yang 1 facilitates the stemness of ovarian cancer via suppressing miR-99a activity through enhancing its deacetylation level. Biomed Pharmacother. 2020;126:110085.

    Article  CAS  Google Scholar 

  17. Shibata M, Hoque MO. Targeting cancer stem cells: a strategy for effective eradication of cancer. Cancers (Basel). 2019;11(5):732.

    Article  CAS  Google Scholar 

  18. Yang Y, Li X, Wang T, Guo Q, Xi T, Zheng L. Emerging agents that target signaling pathways in cancer stem cells. J Hematol Oncol. 2020;13(1):60.

    Article  Google Scholar 

  19. Tumpel S, Rudolph KL. Quiescence: good and bad of stem cell aging. Trends Cell Biol. 2019. https://doi.org/10.1016/j.tcb.2019.05.002.

    Article  PubMed  Google Scholar 

  20. Kobayashi Y, Tanaka T, Mulati M, et al. Cyclin-dependent kinase 1 is essential for muscle regeneration and overload muscle fiber hypertrophy. Front Cell Dev Biol. 2020;8:564581.

    Article  Google Scholar 

  21. Schmidt AK, Pudelko K, Boekenkamp JE, Berger K, Kschischo M, Bastians H. The p53/p73 - p21(CIP1) tumor suppressor axis guards against chromosomal instability by restraining CDK1 in human cancer cells. Oncogene. 2020. https://doi.org/10.1038/s41388-020-01524-4.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gutierrez A, Kim JO, Umbreit NT, et al. Cdk1 phosphorylation of the Dam1 complex strengthens kinetochore-microtubule attachments. Curr Biol. 2020;30(22):4491-4499.e4495.

    Article  CAS  Google Scholar 

  23. Wu G, Lin Q, Lim TK, et al. The interactome of Singapore grouper iridovirus protein ICP18 as revealed by proximity-dependent BioID approach. Virus Res. 2020;291:198218.

    Article  Google Scholar 

  24. Rosendo-Pineda MJ, Vicente JJ, Vivas O, et al. Phosphorylation of NMDA receptors by cyclin B/CDK1 modulates calcium dynamics and mitosis. Commun Biol. 2020;3(1):665.

    Article  CAS  Google Scholar 

  25. Li L, Wang J, Hou J, et al. Cdk1 interplays with Oct4 to repress differentiation of embryonic stem cells into trophectoderm. FEBS Lett. 2012;586(23):4100–7.

    Article  CAS  Google Scholar 

  26. Zhu Y, Li K, Zhang J, Wang L, Sheng L, Yan L. Inhibition of CDK1 reverses the resistance of 5-fu in colorectal cancer. Cancer Manag Res. 2020;12:11271–83.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, 59 Shengli Road, Zhangzhou, 363000, China

    Z. Huang, G. Shen & J. Gao

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  1. Z. Huang
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  2. G. Shen
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  3. J. Gao
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Correspondence to Z. Huang.

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Huang, Z., Shen, G. & Gao, J. CDK1 promotes the stemness of lung cancer cells through interacting with Sox2. Clin Transl Oncol 23, 1743–1751 (2021). https://doi.org/10.1007/s12094-021-02575-z

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  • DOI: https://doi.org/10.1007/s12094-021-02575-z

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