Intestinal Apc ‐inactivation induces HSP25 dependency

Abstract: The majority of colorectal cancers (CRCs) present with early mutations in tumor suppressor gene APC. APC mutations result in oncogenic activation of the Wnt pathway, which is associated with hyperproliferation, cytoskeletal remodeling, and a global increase in mRNA translation. To compensate for the increased biosynthetic demand, cancer cells critically depend on protein chaperones to maintain proteostasis, although their function in CRC remains largely unexplored. In order to investigate the role of molecular chaperones in driving CRC initiation, we captured the transcriptomic profiles of murine wild type and Apc‐mutant organoids during active transformation. We discovered a strong transcriptional upregulation of Hspb1, which encodes small heat shock protein 25 (HSP25). We reveal an indispensable role for HSP25 in facilitating Apc‐driven transformation, using both in vitro organoid cultures and mouse models, and demonstrate that chemical inhibition of HSP25 using brivudine reduces the development of premalignant adenomas. These findings uncover a hitherto unknown vulnerability in intestinal transformation that could be exploited for the development of chemopreventive strategies in high‐risk individuals.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Intestinal Apc ‐inactivation induces HSP25 dependency ; day:02 ; month:11 ; year:2022 ; extent:16 ; EMBO molecular medicine / European Molecular Biology Organization ; (02.11.2022) (gesamt 16)

Contributors, Places and Time

• Creator: van Neerven, Sanne M. ; Smit, Wouter L. ; van Driel, Milou S. ; Kakkar, Vaishali ; de Groot, Nina E. ; Nijman, Lisanne E. ; Elbers, Clara C. ; Léveillé, Nicolas ; Heijmans, Jarom ; Vermeulen, Louis

Further information

• DOI: 10.15252/emmm.202216194
• URN: urn:nbn:de:101:1-2022110214071723549000
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:32 AM CEST