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Fig. 8 | Breast Cancer Research

Fig. 8

From: Glucocorticoid receptors are required effectors of TGFβ1-induced p38 MAPK signaling to advanced cancer phenotypes in triple-negative breast cancer

Fig. 8

GR Ser134 phosphorylation creates a feedforward signaling loop that potentiates further activation of the p38 MAPK pathway downstream of TGFβ1 in TNBC models. Schematic of the conserved three kinase cascade that represents the p38 MAPK module (i.e., MAP3K5, MEK3/6, and p38 MAPK) and known cooperation between 14-3-3ζ and MAP3K5 [50]. Cellular stress as well as TME-derived factors (TGFβ1) input to activation of SMADs and p38 MAPK signaling, resulting in phosphorylation of GR on Ser134. Ligand-independent pS134-GR target genes include key components of the p38 MAPK pathway (MAP3K5) needed for intact p38 signaling. Potential cooperation of 14-3-3ζ and pS134-GR with the SMAD-dependent arm of the TGFβ1 signaling pathway is shown (dotted two-way arch under question mark).

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