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. 2021 Jun 26;40:216. doi: 10.1186/s13046-021-02018-1

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© The Author(s) 2021

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. 3 — HK2 initiates EMT and enhances glucose metabolism in EC cells by activating the FAK/FAK/ERK1/2 pathway and upregulating Twist1 and Snail expression. a The top 100 genes that show a positive or negative co-expression correlation with HK2 in the TCGA EC dataset were selected and uploaded to Metascape for GO term detection and clustering. Same-colored dots fall into a function similar to the given title. Only the top 20 significant GO categories were shown. b Pearson correlation analysis revealed that HK2 was significantly correlated with FAK in the TCGA EC dataset using LinkedOmics. c Analysis of FAK levels in EC and normal tissues using the TCGA data from UALCAN. d The protein expression of FAK in EC and adjacent normal tissues. Images were downloaded from Human Protein Atlas. e The microarray dataset (GSE17025) was analyzed for FAK expression in stage I EC samples and normal endometrium samples. f Kaplan-Meier curves show the overall survival of EC patients with high or low FAK expression from KM Plotter. g Western blotting analysis of FAK expression in a normal endometrial cell line (EM) and human EC cell lines, including Ishikawa, HEC-1, HEC-50, and sphere-forming (sphere) or TX-resistant (TX) HEC-50 derivatives. h Western blotting analysis of the indicated proteins in EC cells following overexpression or knockdown of HK2. i Western blotting analysis of the indicated proteins in Ishikawa cells expressing HK2, in the presence or absence of FAK inhibitor PF-573,228 (PF). j, k, l Cell migration, invasion, sphere formation, glucose consumption, and lactate production of Ishikawa cells expressing the control vector or HK2 vector, in the presence or absence of FAK inhibitor PF. m Ishikawa cells were transfected with or without the HK2 vector and treated with TX. Cell survival was examined by a cell viability assay in the presence or absence of PF. Ishi: Ishikawa; vec: vector; sh: shRNA. *P < 0.05