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Fig. 11 | Cell Communication and Signaling

Fig. 11

From: Minocycline impairs TNF-α-induced cell fusion of M13SV1-Cre cells with MDA-MB-435-pFDR1 cells by suppressing NF-κB transcriptional activity and its induction of target-gene expression of fusion-relevant factors

Fig. 11

Schematic model of how minocycline may inhibit TNF-α-induced cell fusion. The intracellular signal transduction pathway by TNF-α was investigated in this study. When TNF-α binds to TNFR1, the downstream signal cascade is activated via TRAF2 recruitment and IκBα kinase complexes resulting in the release of the transcription factor NF-κB in M13SV1-Cre cells. Conjointly, the TNFR1-SRC interaction is abrogated during the signal processing of TNFR1-TRAF2. Minocycline inhibits TNFR1/TRAF2/IKK/IκBα/NF-κB signalling activity in M13SV1 cells, thereby suppressing the NF-κB-regulated target gene expression of putative cell fusion factors, such as MMP9 and ICAM1. Furthermore, SRC and TNFR1 expression was also suppressed by minocycline in M13SV1-Cre cells, which may additionally contribute to an impaired TNF-α induced TNFR1-NF-κB signalling. In contrast to M13SV1-Cre cells, minocycline in combination with TNF-α induces high NF-κB-regulated ICAM1 expression in MDA-MB-435-pFDR1 cancer cells. It is suggested that the release of MMP9 is responsible for the ICAM1 surface shedding that reduces the distance of the fusion partners, thus facilitating membrane merging and the initiation of the fusion process

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