%0 Journal Article
%T β2-microglobulin induced apoptosis of tumor cells via the ERK signaling pathway by directly interacting with HFE in HER2-overexpressing breast cancer.
%A Li K
%A Chai D
%A Ren S
%A Lian X
%A Shi X
%A Xu Y
%A Bao L
%A Yang S
%A Liang Y
%A Li X
%A Du H
%J BMC Cancer
%V 24
%N 1
%D 2024 Aug 12
%M 39128984
%F 4.638
%R 10.1186/s12885-024-12757-x
%X <B>BACKGROUND: </B>Our previous study demonstrated that β2-microglobulin (β2M) promoted ER+/HER2- breast cancer survival via the SGK1/Bcl-2 signaling pathway. However, the role of β2M has not been investigated in ER-/HER2+ breast cancer. Here, we aimed to determine the role of β2M in ER-/HER2+ breast cancer.<BR><B>METHODS: </B>The interaction between β2M and HFE was confirmed by co-immunoprecipitation, mass spectrometry, yeast two-hybrid screening, and His pull-down. The knockdown and overexpression of β2M or HFE were performed in MDA-MB-453 cells, and ERK signaling pathway was subsequently analyzed via western blotting. Apoptotic cells were detected using flow cytometer. β2M, HFE, and p-ERK1/2 were examined in tumor and paired adjacent tissues via immunohistochemistry.<BR><B>RESULTS: </B>HFE was found to be an interacting protein of β2M in ER-/HER2+ breast cancer cells MDA-MB-453 by co-immunoprecipitation and mass spectrometry. A yeast two-hybrid system and His-pull down experiments verified that β2M directly interacted with HFE. β2M and HFE as a complex were mainly located in the cytoplasm, with some on the cytomembrane of MDA-MB-453 cells. 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 by interacting with HFE and induced apoptosis of MDA-MB-453 cells. The expression of HFE and p-ERK1/2 showed significantly high levels in HER2-overexpressing breast cancer tumor tissue compared with adjacent normal tissue, consistent with the results obtained from the cell experiments.<BR><B>CONCLUSIONS: </B>β2M induced apoptosis of tumor cells via activation of the ERK signal pathway by directly interacting with HFE in HER2-overexpressing breast cancer.