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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. 2 — a Protein expressions of RANK were detected by western blot analysis in seven CRC cell lines. b, c RANK stable overexpression or knockdown efficiency was confirmed by western blotting in CRC cells. d, e RANK overexpression promoted the migration and invasion of SW480 and Caco2 cells. And the addition of 100 ng/ml RANKL moderately increased the migration and invasion of RANK-overexpressing SW480 and Caco2 cells. Scales bars = 100 μm. f Knockdown of RANK inhibited the migration and invasion of HT29 cells. Scales bars = 100 μm. g Bioluminescent images of representative mice at week 15 after implantation. h The total tumor burden is quantified as total photons measured by bioluminescent technology. i Livers were excised for ex vivo bioluminescent imaging. j Representative results for staining of metastatic nodules (black arrows) in the livers. Scales bars = 500 μm (40×), 200 μm (100×). k The statistical analyses of metastatic nodules. Data are mean ± SD (n = 3; n = 6 mice/group for in vivo experiments). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.