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. 2020 Oct 15;39:217. doi: 10.1186/s13046-020-01713-9

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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. 7 — Inhibition of MAPK signalling improves response to alpelisib. a Effect of P90RSK inhibitor BI-D1870 and alpelisib (5 μM each) on viability of alpelisib-resistant cell lines. * represents p < 0.05, ** represents p < 0.01, **** represents p < 0.0001. One-way ANOVA. b Immunoblot of MAPK pathway members following knockdown of AXL and TYRO3. siCT = scrambled control siRNA. Densitometric quantification of each protein relative to α-tubulin is shown below each band. c Dose response curve comparing sensitivity of parental and alpelisib-resistant PDX-C cells to alpelisib. d Immunoblot of parental and alpelisib-resistant PDX-C cell lysates for expression of TYRO3 and AXL RTKs. Densitometric quantification of each protein relative to α-tubulin is shown below each band. e Flow cytometric analysis of AXL and TYRO3 in parental and resistant PDX-C cells. Median fluorescence intensity (MFI) was measured and graphed for three biological replicates. * represents p < 0.05, ns = not significant, unpaired Student’s t-test. f Immunoblot of parental and alpelisib-resistant PDX-C cell lysates for activation of the MAPK pathway. Densitometric quantification of each protein relative to α-tubulin is shown below each band