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Article

Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway

  • Authors:
    • Ai-Ni Tsao
    • Yu-Syuan Chuang
    • Yen-Chun Lin
    • Yeu Su
    • Ta-Chung Chao
  • View Affiliations / Copyright

    Affiliations: Institute of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 11200, Taiwan, R.O.C., Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11200, Taiwan, R.O.C.
  • Article Number: 105
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    Published online on: April 12, 2022
       https://doi.org/10.3892/or.2022.8316
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Abstract

Cyclin‑dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy are the current standard of care used in the first‑line treatment of hormone receptor‑positive/HER2‑negative metastatic breast cancer (BC). Although CDK4/6 inhibitors mainly target the cell cycle, emerging evidence has indicated further potential roles of CDKs other than regulating cell cycle progression. The G1 and G2/M transition regulators, including cyclins D and E, as well as their catalytic partners, CDK2, CDK4 and CDK6, have been reported to play crucial roles in pluripotency maintenance and cell fate decisions of human pluripotent stem cells by controlling transcription factors, signaling pathways and epigenetic regulators. Dinaciclib, a CDK1/2/5/9 inhibitor, is currently being evaluated in clinical trials against various cancer types, including BC. However, the underlying molecular mechanisms of CDK1/2/5/9 inhibitors in regulating BC stemness remain poorly understood. The present study aimed to examine the stemness‑inhibitory effects of dinaciclib in MCF‑7 (luminal) and HCC‑1806 (triple‑negative) BC cells. We found that this drug not only effectively reduced the self‑renewal abilities and other malignant properties, but also dose‑dependently decreased the protein expression levels of three BC stem cell markers, CD44, aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and BMI1 proto‑oncogene, polycomb ring finger (Bmi1), as well as three embryonic stem cell markers, Oct4, Nanog and Sox2. Moreover, the dinaciclib‑induced decrease of Oct4 and Nanog protein expression was able to be restored by co‑treatment with MG‑132, a proteasome inhibitor. Forkhead box M1 (FoxM1), both a stemness‑stimulating transcription factor and a cell cycle regulator, along with the Hedgehog signaling pathway, were identified as the therapeutic targets of dinaciclib. Collectively, the present results demonstrated a novel role of dinaciclib in suppressing BC stemness and indicated its potential use for future cancer treatments.
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Copy and paste a formatted citation
Spandidos Publications style
Tsao A, Chuang Y, Lin Y, Su Y and Chao T: Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway. Oncol Rep 47: 105, 2022.
APA
Tsao, A., Chuang, Y., Lin, Y., Su, Y., & Chao, T. (2022). Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway. Oncology Reports, 47, 105. https://doi.org/10.3892/or.2022.8316
MLA
Tsao, A., Chuang, Y., Lin, Y., Su, Y., Chao, T."Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway". Oncology Reports 47.5 (2022): 105.
Chicago
Tsao, A., Chuang, Y., Lin, Y., Su, Y., Chao, T."Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway". Oncology Reports 47, no. 5 (2022): 105. https://doi.org/10.3892/or.2022.8316
Copy and paste a formatted citation
x
Spandidos Publications style
Tsao A, Chuang Y, Lin Y, Su Y and Chao T: Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway. Oncol Rep 47: 105, 2022.
APA
Tsao, A., Chuang, Y., Lin, Y., Su, Y., & Chao, T. (2022). Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway. Oncology Reports, 47, 105. https://doi.org/10.3892/or.2022.8316
MLA
Tsao, A., Chuang, Y., Lin, Y., Su, Y., Chao, T."Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway". Oncology Reports 47.5 (2022): 105.
Chicago
Tsao, A., Chuang, Y., Lin, Y., Su, Y., Chao, T."Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway". Oncology Reports 47, no. 5 (2022): 105. https://doi.org/10.3892/or.2022.8316
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