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. 2019 Sep 9;39(3):530–545. doi: 10.1038/s41388-019-0962-8

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© The Author(s) 2019

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. 6 — Targeting TR4/lncTASR/AXL signaling with tretinoin can increase sunitinib sensitivity to better suppress the RCC progression. a Tretinoin alone was not toxic to RCC cells. b Tretinoin can enhance the sensitivity of RCC to sunitinib when combined with low dose sunitinib. c Tretinoin actually has synergetic effects when combined with sunitinib in the treatment of RCC cells. d Western blotting (left) with quantification (right) shows that the expression of both TR4 and AXL decreased after treated with tretinoin. e Tretinoin can reverse the resistance of RCC cells to sunitinib caused by overexpressed TR4. f Viability of OSRC-2 cells in sunitinib with/without tretinoin and with/without TR4-shRNA. g DID (difference in difference) analysis shows that TR4-knockdown OSRC-2 cells have less difference change in sunitinib resistance with/without tretinoin compared with OSRC-2 cells without TR4-knockdown. h Tretinoin decreases both TR4 and AXL protein expressions in OSRC-2 cells with pLKO vehicle, but does not decrease TR4 and AXL expressions in TR4-knockdown OSRC-2 cells. Data is presented as Mean ± s.e.m., **p < 0.01, ***p < 0.001, ns not significant