TY - JOUR
T1 - Therapeutic gene silencing of CKAP5 leads to lethality in genetically unstable cancer cells
AU - Chatterjee, Sushmita
AU - Naidu, Gonna Somu
AU - Hazan-Halevy, Inbal
AU - Grobe, Hanna
AU - Ezra, Assaf
AU - Sharma, Preeti
AU - Goldsmith, Meir
AU - Ramishetti, Srinivas
AU - Sprinzak, David
AU - Zaidel-Bar, Ronen
AU - Peer, Dan
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
PY - 2023/4/7
Y1 - 2023/4/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85151791803&partnerID=8YFLogxK
U2 - 10.1126/sciadv.ade4800
DO - 10.1126/sciadv.ade4800
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C2 - 37018392
AN - SCOPUS:85151791803
SN - 2375-2548
VL - 9
JO - Science advances
JF - Science advances
IS - 14
M1 - eade4800
ER -
