Lbh, or Limb-bud and Heart, is a transcription co-factor that is essential for multiple biological processes. It is involved in the WNT pathway and has significance in the development of various tissues. Genetic models, such as gene knockout mice, have been crucial in understanding its functions [1,3].

In triple-negative breast cancer (TNBC), blocking LBH expression causes replication stress due to DNA replication fork stalling, leading to apoptotic cell death and S-G2M cell cycle delays. ATR inhibition combined with LBH downmodulation has a synergistic effect in killing TNBC cells [1]. In cochlear hair cells, Lbh-null mice show progressive hearing loss with stereocilia bundle degeneration and outer hair cell loss, indicating LBH is necessary for hair cell survival [3]. In glioma, LBH promotes cell proliferation, migration, invasion, and in vivo tumor growth, with its upregulation correlating with poor patient survival [2].

In conclusion, LBH plays essential roles in maintaining genome integrity in cancer cells, survival of cochlear hair cells, and progression of glioma. Studies using gene knockout mouse models have been pivotal in revealing these functions, offering potential therapeutic targets for TNBC, hearing loss, and glioma.

References:

1. Garikapati, Koteswararao, Young, In-Chi, Hong, Sunhwa, Jain, Chaitanya, Briegel, Karoline J. 2024. Blocking LBH expression causes replication stress and sensitizes triple-negative breast cancer cells to ATR inhibitor treatment. In Oncogene, 43, 851-865. doi:10.1038/s41388-024-02951-3. https://pubmed.ncbi.nlm.nih.gov/38297083/

2. Liu, Luotong, Luo, Qinglian, Xu, Qian, Xiong, Yu, Deng, Huajiang. 2021. Limb-bud and heart development (LBH) contributes to glioma progression in vitro and in vivo. In FEBS open bio, 12, 211-220. doi:10.1002/2211-5463.13325. https://pubmed.ncbi.nlm.nih.gov/34739189/

3. Liu, Huizhan, Giffen, Kimberlee P, Grati, M'Hamed, Briegel, Karoline J, He, David Z. 2021. Transcription co-factor LBH is necessary for the survival of cochlear hair cells. In Journal of cell science, 134, . doi:10.1242/jcs.254458. https://pubmed.ncbi.nlm.nih.gov/33674448/