Hsp90 inhibitor sensitizes TRAIL-mediated apoptosis via chop-dependent DR5 upregulation in colon cancer cells.
Year: 2017
Type: article
Abstract: Heat shock protein 90 (Hsp90), a molecular chaperone, is involved in a variety of physiological and pathological processes. Targeting Hsp90 by small molecules has been developed as an attractive strategy of anticancer therapy. In this study, we investigated the mechanism of Hsp90 inhibitor suppresses CRC growth and potentiates effects of other chemotherapeutic drugs. We found that Hsp90 inhibitor induces chop-dependent DR5 upregulation regardless of p53 status. Furthermore, DR5 is required for Hsp90 inhibitor-induced apoptosis. Hsp90 inhibitor also synergized with TRAIL to induce marked apoptosis via DR5 in CRC. Overall, our results illustrate DR5 play a key role in mediating the anticancer effects of Hsp90 inhibitor in CRC and suggest that DR5 expression can be used as an indicator of Hsp90 inhibitor sensitivity, which has important implications for it clinical applications.
Source: PubMed
Authors: Zhicheng Yao, Ang Chen, Xin Li, Zhiyong Zhu, Xin Jiang
Institution: Liaoning Provincial People's Hospital
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3008425152