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

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 3, 2024

Abstract There are significant commonalities among several pathologies involving fibroblasts, ranging from auto-immune diseases to fibrosis and cancer. Early steps in cancer development progression closely linked fibroblast senescence transformation into tumor-promoting cancer-associated fibroblasts (CAFs), suppressed by the androgen receptor (AR). Here, we identify ANKRD1 as a mesenchymal-specific transcriptional coregulator under direct AR negative control human dermal (HDFs) key driver of CAF conversion, independent cellular senescence. expression CAFs is associated with poor survival HNSCC, lung, cervical SCC patients, controls specific gene program myofibroblast (my-CAFs). binds regulatory region my-CAF effector genes concert AP-1 transcription factors, promotes c-JUN FOS association. Targeting disrupts complex formation, reverses activation, blocks pro-tumorigenic properties an orthotopic skin model. thus represents target for fibroblast-directed therapy potentially beyond.

Language: Английский

Insights into Tumor Size-Dependent Nanoparticle Accumulation Using Deformed Organosilica Nanoprobes

Materials Chemistry Frontiers, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Deformed organosilica nanoprobes (CDPF) exhibit enhanced accumulation within larger tumors, highlighting the pivotal role of tumor microenvironment in optimization nanoparticle-based therapeutic strategies.

Language: Английский