HSP90 as a regulator of extracellular matrix dynamics

The extracellular matrix (ECM) is a dynamic and organised extracellular network assembled from proteins and carbohydrates exported from the cell. The ECM is critical for multicellular life, providing spatial and temporal cellular cues to maintain tissue homeostasis. Consequently, ECM production must be carefully balanced with turnover to ensure homeostasis; ECM dysfunction culminates in disease. Hsp90 is a molecular chap-erone central to protein homeostasis, including in the ECM. Intracellular and extracellular Hsp90 isoforms collaborate to regulate the levels and status of proteins in the ECM via multiple mechanisms. In so doing, Hsp90 regulates ECM dynamics, and changes in Hsp90 levels or activity support the development of ECM-related diseases, like cancer and fibrosis. Consequently, Hsp90 levels may have prognostic value, while inhibition of Hsp90 may have therapeutic potential in conditions characterised by ECM dysfunction.

Automated summary

The extracellular matrix (ECM) is vital for maintaining tissue homeostasis by providing cellular cues, and imbalance in ECM production and turnover can lead to diseases. Hsp90 plays a central role in regulating protein homeostasis, including in the ECM, and changes in its levels or activity can contribute to ECM-related diseases. Prognostic value of Hsp90 levels and potential therapeutic benefits of its inhibition in conditions associated with ECM dysfunction are being explored.