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Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer

  • Authors:
    • Jong Seung Lim
    • Eunkyoung Kim
    • Jin-Sook Song
    • Sunjoo Ahn
  • View Affiliations / Copyright

    Affiliations: Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea
    Copyright: © Lim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 101
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    Published online on: June 21, 2024
       https://doi.org/10.3892/or.2024.8760
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Abstract

Monopolar spindle 1 kinase (Mps1, also known as TTK protein kinase) inhibitors exert marked anticancer effects against triple‑negative breast cancer (TNBC) by causing genomic instability and cell death. As aneuploid cells are vulnerable to compounds that induce energy stress through adenosine monophosphate‑activated protein kinase (AMPK) activation, the synergistic effect of Mps1/TTK inhibition and AMPK activation was investigated in the present study. The combined effects of CFI‑402257, an Mps1/TTK inhibitor, and AICAR, an AMPK agonist, were evaluated in terms of cytotoxicity, cell‑cycle distribution, and in vivo xenograft models. Additional molecular mechanistic studies were conducted to elucidate the mechanisms underlying apoptosis and autophagic cell death. The combination of CFI‑402257 and AICAR showed selective cytotoxicity in a TNBC cell line. The formation of polyploid cells was attenuated, and apoptosis was increased by the combination treatment, which also induced autophagy through dual inhibition of the PI3K/Akt/mTOR and mitogen‑activated protein kinase (MAPK) signaling pathways. Additionally, the combination therapy showed strongly improved efficacy in comparison with CFI‑402257 and AICAR monotherapy in the MDA‑MB‑231 xenograft model. The present study suggested that the combination of CFI‑402257 and AICAR is a promising therapeutic strategy for TNBC.
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Copy and paste a formatted citation
Spandidos Publications style
Lim JS, Kim E, Song J and Ahn S: Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer. Oncol Rep 52: 101, 2024.
APA
Lim, J.S., Kim, E., Song, J., & Ahn, S. (2024). Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer. Oncology Reports, 52, 101. https://doi.org/10.3892/or.2024.8760
MLA
Lim, J. S., Kim, E., Song, J., Ahn, S."Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer". Oncology Reports 52.2 (2024): 101.
Chicago
Lim, J. S., Kim, E., Song, J., Ahn, S."Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer". Oncology Reports 52, no. 2 (2024): 101. https://doi.org/10.3892/or.2024.8760
Copy and paste a formatted citation
x
Spandidos Publications style
Lim JS, Kim E, Song J and Ahn S: Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer. Oncol Rep 52: 101, 2024.
APA
Lim, J.S., Kim, E., Song, J., & Ahn, S. (2024). Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer. Oncology Reports, 52, 101. https://doi.org/10.3892/or.2024.8760
MLA
Lim, J. S., Kim, E., Song, J., Ahn, S."Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer". Oncology Reports 52.2 (2024): 101.
Chicago
Lim, J. S., Kim, E., Song, J., Ahn, S."Energy‑stress‑mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple‑negative breast cancer". Oncology Reports 52, no. 2 (2024): 101. https://doi.org/10.3892/or.2024.8760
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