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. 2022 Jun 23;27(2):145–153. doi: 10.1007/s10911-022-09521-x

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© The Author(s) 2022

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/.

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Fig. 2 — SHP2/MAPK enhances IL-8 levels via the transcription factor ETS1. (A) Scatter plot representing ranked phospho-tyrosine peptides depleted (left) or enriched (right) in SUM159 cells after 30 min of SHP099 treatment. Dark blue dots indicate phospho-peptides known to be involved in MAPK pathway regulation. The dotted line represents an arbitrary cutoff value. (B–C) Curves representing IL-8 protein abundance in the supernatants of the indicated cell lines upon MEK162 treatment at the indicated time points. Data shown are IL-8 protein concentrations normalized by total protein. Fold changed based on the 2h time point, ± S.D. (n = 3, ***P ≤ 0.001, ****P ≤ 0.0001, Two-way ANOVA test). (D) Bar graphs showing the ETS1 transcription factor activity profile (left) in SHP2 knockdown SUM159 tumors and MCF10A-HER2/HER3 3D cultures and its DNA-binding motif (right). (E) Bar graphs representing ETS1 and CXCL8 mRNA expression in the indicated cell lines 96 h after addition of siRNA (n = 3, *P ≤ 0.05, ***P ≤ 0.001, Two-way ANOVA test)