β‑catenin blockers enhance the effect of CDK4/6 inhibitors on stemness and proliferation suppression in endocrine‑resistant breast cancer cells

Ahrong Ham, Min Hee Cho, Hye Sung Won, Jungmin Jo, Kyoung Eun Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Wnt/β-catenin signaling is involved in endocrine resistance and stem cell-like properties of hormone receptor-positive breast cancer cells. Palbociclib is a well-known inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6 inhibitor) that downregulates the activation of retinoblastoma protein, thereby inhibiting the cell cycle in breast cancer cells. The inhibitory effects of a combination of palbociclib and ICG-001, a β-catenin small-molecule inhibitor, were investigated in tamoxifen-resistant breast cancer cell lines. Tamoxifen-resistant MCF-7 (TamR) cells were established by continuously exposing MCF-7 cells to tamoxifen. The characteristics associated with the stem cell-like property of cancer were assessed using western blotting, cell cycle analysis, and the mammosphere assay. The effects of the combination of palbociclib and ICG-001 were evaluated in control MCF-7 and TamR cell lines. Compared with control cells, TamR cells exhibited elevated levels of Nanog, Sox2, ALDH1, and p-STAT3, indicating stem cell-like characteristics, and elevated β-catenin activity. TamR cells also showed significantly higher mammosphere-forming efficiency.

Original languageEnglish
Article number130
JournalOncology Reports
Volume48
Issue number1
DOIs
StatePublished - Jul 2022

Bibliographical note

Funding Information:
The present study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (grant no. NRF‑2017R1D1A1B04035892).

Publisher Copyright:
© 2022 Spandidos Publications. All rights reserved.

Keywords

  • ICG-001
  • breast cancer
  • cyclin-dependent kinase 4 and 6 inhibitor
  • endocrine resistance
  • signal transducer and activator of transcription 3
  • stemness
  • β-catenin

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