LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer
2024

LKB1 Inactivation and Prostate Cancer Resistance

Sample size: 6 publication 10 minutes Evidence: high

Author Information

Author(s): Li Fei, Dai Pengfei, Shi Huili, Zhang Yajuan, He Juan, Gopalan Anuradha, Li Dan, Chen Yu, Du Yarui, Xu Guoliang, Yang Weiwei, Liang Chao, Gao Dong

Primary Institution: Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China

Hypothesis

LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer.

Conclusion

LKB1 inactivation leads to AR-independent lineage plasticity and global DNA hypomethylation during prostate cancer progression.

Supporting Evidence

  • LKB1 inactivation is linked to AR independence in prostate cancer cells.
  • Pharmacological inhibition of TET enzymes effectively suppresses AR-independent prostate cancer growth.
  • Global DNA hypomethylation is induced by LKB1 loss, contributing to lineage plasticity.

Takeaway

When a specific gene called LKB1 is turned off in prostate cancer, the cancer cells can change into a form that doesn't respond to usual treatments, making it harder to treat.

Methodology

The study utilized single-cell RNA sequencing on human and mouse prostate cancer samples, whole-genome bisulfite sequencing, and genetically engineered mouse models.

Statistical Information

P-Value

p<0.05

Digital Object Identifier (DOI)

10.1038/s41422-024-01025-z

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