Fig. 9: Schematic representation of the role of ANKRD1 in CAF activation and potential translational relevance. | Nature Communications

Fig. 9: Schematic representation of the role of ANKRD1 in CAF activation and potential translational relevance.

From: ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation

Fig. 9

AR binding to the promoter of the ANKRD1 gene and suppresses its expression (1). Downmodulation of AR at early steps of CAF activation leads to upregulation of ANKRD1 (2). ANKRD1 associates with the AP1 (JUN-FRA2) transcriptional complex and promotes AP1-dependent expression of CAF effector genes (3). Direct targeting of ANKRD1 through stabilized anti-sense oligonucleotides (ASOs), or indirect targeting of ANKRD1 by the AP1 inhibitor T-5224 (4) disrupt the AP1 transcriptional complex and reverses CAF activation (5), suppressing cancer-stromal cell expansion. Created with Biorender.com (https://www.biorender.com/).

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