Fig. 1: a STING-dependent paclitaxel-induced secretome spreads BCL-xL apoptotic priming. | Nature Communications

Fig. 1: a STING-dependent paclitaxel-induced secretome spreads BCL-xL apoptotic priming.

From: STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment

Fig. 1

a, b STAT1 and NF-κB pathway analysis of 24 h-paclitaxel treated or not STING−/− (a) and cGAS−/− (b) or control MDA-MB-468 cells by immunoblotting. c Representative pictures of cGAS immunostaining (left panel, scale bar: 20 µm) and quantification of micronucleated cells (middle panel) and cGAS-positive micronuclei (left panel) in control or LMNB2 overexpressing MDA-MB-468 cells after paclitaxel treatment. d cGAS-positive micronucleated cells quantification in paclitaxel-treated or not in PDX #248 and PDX#249 (lower panel) and representative fields after IHC staining with anti-cGAS (upper panel; scale bar: 50 µm). e STAT1 and NF-κB pathway immunoblot analysis in paclitaxel-treated or not, LMNB2 overexpressing or control MDA-MB-468 cells. f 24 h-paclitaxel treated or not (donor) cells were washed out to produce 48 h-conditioned media (CM) that were applied to untreated (recipient) corresponding cancer cells for 48 h in presence or not of the BH3 mimetics WEHI-539, ABT-199, or S63845. Apoptotic index in recipient breast cancer cells was assessed using Annexin-V staining. g–i Same experiment as (f) using control or STING−/− (g) or cGAS−/− (h) or LMNB2 overexpressing (i) indicated donor cells in presence of the BH3 mimetic WEHI-539 or not. j Cell viability of PDX #306 cultured in organoids (BC-PDX#306) in paclitaxel-treated conditions for 4 days and ABT-737 or ABT-199 BH3 mimetics added for the 2 last days (sequential treatment). k Cell viability of 3 distinct patient-derived organoids (BC-01, BC-02, and BC-03) in ABT-737-treated conditions plus paclitaxel or cGAMP. l 24 h-paclitaxel-pretreated control or STING−/− MDA-MB-468 cells were cultured with untreated MDA-MB-468 H2B-RFP expressing cells. After 48 h, co-cultures were treated or not with WEHI-539 for additional 48 h and cell death was assessed in each cell population. Error bars indicate mean +/− SEM; Two-sided paired t-test. The symbols correspond to a p-value inferior to *0.05, **0.01, and ***0.001. NS: not significant. Data were collected from n = 3 independent experiments except d (n = 5).

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