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. 2021 Apr 1;12(4):336. doi: 10.1038/s41419-021-03642-7

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© The Author(s) 2021

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — Active RANK expression allows for Ca²⁺ release from ER dependent on PLCγ-mediated IP3R and Ca²⁺ influx from the extracellular milieu through STIM1-regulated SOCE. Besides, PLCγ-mediated IP3R axis act upstream of STIM1 to coactivate Ca²⁺ oscillation. The Ca²⁺ oscillation in the cytoplasm leads to calcium-dependent calcineurin activation and NFATC1 transcription of osteoclast-specific gene, ACP5, which promotes CRC metastasis. PLCγ phospholipase C γ, IP3R inositol-1,4,5-trisphosphate receptor, SOCE store-operated calcium entry, STIM stromal interaction molecule, TRPC transient receptor potential channel, NFATC1 nuclear factor of activated T cells c1, CsA cyclosporine A, 2APB 2-aminoethoxydiphenyl-borate, ACP5 tartrate-resistant acid phosphatase 5, ER endoplasmic reticulum.