Therapeutic gene silencing of CKAP5 leads to lethality in genetically unstable cancer cells

Sushmita Chatterjee, Gonna Somu Naidu, Inbal Hazan-Halevy, Hanna Grobe, Assaf Ezra, Preeti Sharma, Meir Goldsmith, Srinivas Ramishetti, David Sprinzak, Ronen Zaidel-Bar, Dan Peer

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The potential of microtubule-associated protein targets for cancer therapeutics remains largely unexplored due to the lack of target-specific agents. Here, we explored the therapeutic potential of targeting cytoskeleton-associated protein 5 (CKAP5), an important microtubule-associated protein, with CKAP5-targeting siRNAs encapsulated in lipid nanoparticles (LNPs). Our screening of 20 solid cancer cell lines demonstrated selective vulnerability of genetically unstable cancer cell lines in response to CKAP5 silencing. We identified a highly responsive chemo-resistant ovarian cancer cell line, in which CKAP5 silencing led to significant loss in EB1 dynamics during mitosis. Last, we demonstrated the therapeutic potential in an in vivo ovarian cancer model, showing 80% survival rate of siCKAP5 LNPs-treated animals. Together, our results highlight the importance of CKAP5 as a therapeutic target for genetically unstable ovarian cancer and warrants further investigation into its mechanistic aspects.

Original languageEnglish (US)
Article numbereade4800
Pages (from-to)eade4800
JournalScience advances
Volume9
Issue number14
DOIs
StatePublished - Apr 5 2023

Keywords

  • Humans
  • Animals
  • Female
  • Gene Silencing
  • Microtubule-Associated Proteins/metabolism
  • RNA, Small Interfering/genetics
  • Microtubules/metabolism
  • Ovarian Neoplasms/genetics
  • Nanoparticles

ASJC Scopus subject areas

  • General

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