KEY TAKEAWAYS
- The study aimed to investigate β2M’s role in ER–/HER2+ breast cancer and its effects on tumor behavior.
- β2M induces apoptosis in HER2-overexpressing breast cancer cells by activating the ERK pathway through HFE interaction.
Previous research revealed that β2-microglobulin (β2M) enhances survival in ER+/HER2– breast cancer through the SGK1/Bcl-2 signaling pathway. However, the function of β2M in ER–/HER2+ breast cancer remains unexplored.
Kesheng Li and the team aimed to explore the role of β2M in ER–/HER2+ breast cancer, assessing its potential impact on tumor behavior and survival in this specific subtype.
Researchers confirmed the interaction between β2M and HFE using various techniques, including co-immunoprecipitation and mass spectrometry. They manipulated β2M and HFE levels in MDA-MB-453 cells and analyzed ERK signaling with western blotting. Apoptosis was measured using flow cytometry. Lastly, they examined β2M, HFE, and p-ERK1/2 in tumor and adjacent tissues with immunohistochemistry.
The results indicated that in MDA-MB-453 ER-/HER2+ breast cancer cells, β2M was confirmed to interact with HFE through co-immunoprecipitation and mass spectrometry. This interaction was further validated by yeast two-hybrid and His-pull-down experiments. Both β2M and HFE were mainly found in the cytoplasm and on the cell membrane.
In addition to breast cancer cells BT474, endogenous β2M directly interacted with HFE in breast cancer cells MDA-MB-453, MDA_mB-231, and MCF-7. β2M activated the ERK signaling pathway and triggered apoptosis in MDA-MB-453 cells. Higher levels of HFE and p-ERK1/2 were found in HER2- overexpressing breast cancer tissue compared to adjacent normal tissue, aligning with cell experiment results.
The study concluded that β2M induces apoptosis in HER2-overexpressing breast cancer cells by activating the ERK signaling pathway through direct interaction with HFE.
Funding support was provided by the Natural Science Foundation of Gansu and the Health Scientific Research Plan of Gansu.
Source: https://pubmed.ncbi.nlm.nih.gov/39128984/.
Li K, Chai D, Ren S, et al. (2024). “β2-microglobulin induced apoptosis of tumor cells via the ERK signaling pathway by directly interacting with HFE in HER2-overexpressing breast cancer.” BMC Cancer. 2024 Aug 12;24(1):991. doi: 10.1186/s12885-024-12757-x. PMID: 39128984.
