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. 2020 Sep 7;8:39. doi: 10.1186/s40364-020-00223-2

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — The interaction between ERβ and PI3-K/Akt signaling. Heregulin-β binds to HER2/HER3 receptors, which leading to the PI3-K/Akt signaling activation. The enhancement of PI3-K/Akt signaling triggers the recruitment of the E3 ubiquitin ligase MDM2 to ERβ, which is further stabilized by CBP, resulting in ERβ polyubiquitination. On the contrary, expression of ERβ results in a decrease in Akt signaling by increasing PTEN levels and decreasing protooncogene HER2/HER3 signaling