Europe PMC
Nothing Special   »   [go: up one dir, main page]

Europe PMC requires Javascript to function effectively.

Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page.

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Targeting AURKA to induce synthetic lethality in CREBBP-deficient B-cell malignancies via attenuation of MYC expression.

Show less

Author information

Affiliations

  • 1. Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
      Authors
    • Sun Y 1, 2
    (1 author)
  • 2. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
      Authors
    • Sun Y 1, 2
    • Chen J 2
    • Xiao R 2
    • Wang P 2
    • Deng P 2
    • Gao J 2
    • Wang Y 2
    • Tan J 2
    (8 authors)
  • 3. Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore.
      Authors
    • Hong JH 3
    • Teh BT 3
    • Yu Q 3
    • Ong CK 3, 7
    (4 authors)
  • 4. Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology Guangzhou, Guangzhou, China.
      Authors
    • Teng Y 4
    • Pan L 4
    • Liu L 4
    • Liu S 4
    • Li W 4
    (5 authors)
  • 5. Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, China.
      Authors
    • Yu Z 5
    (1 author)
    • Show all (9)

ORCIDs linked to this article

Show all (8)

Oncogene, 23 May 2024, 43(28):2172-2183
https://doi.org/10.1038/s41388-024-03065-6 PMID: 38783101 

Abstract 

Loss-of-function mutations in CREBBP, which encodes for a histone acetyltransferase, occur frequently in B-cell malignancies, highlighting CREBBP deficiency as an attractive therapeutic target. Using established isogenic cell models, we demonstrated that CREBBP-deficient cells are selectively vulnerable to AURKA inhibition. Mechanistically, we found that co-targeting CREBBP and AURKA suppressed MYC transcriptionally and post-translationally to induce replication stress and apoptosis. Inhibition of AURKA dramatically decreased MYC protein level in CREBBP-deficient cells, implying a dependency on AURKA to sustain MYC stability. Furthermore, in vivo studies showed that pharmacological inhibition of AURKA was efficacious in delaying tumor progression in CREBBP-deficient cells and was synergistic with CREBBP inhibitors in CREBBP-proficient cells. Our study sheds light on a novel synthetic lethal interaction between CREBBP and AURKA, indicating that targeting AURKA represents a potential therapeutic strategy for high-risk B-cell malignancies harboring CREBBP inactivating mutations.

Full text links 

Read article at publisher's site: https://doi.org/10.1038/s41388-024-03065-6

References 

Articles referenced by this article (41)

Show 10 more references (10 of 41)

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Funding 

Funders who supported this work.

Guangzhou Municipal Science and Technology Project (1)

National Natural Science Foundation of China (National Science Foundation of China) (5)