Creb1, also known as cAMP responsive element binding protein 1, is a key transcription factor. It mediates transcriptional responses to various growth factors and stress signals, playing a critical role in tumor development and progression. It is involved in multiple pathways, such as those related to immune responses, cell proliferation, and metabolism [3]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In skin inflammation, CREB1 drives the development of CXCR4hi neutrophils. Blockade of CXCR4hi neutrophils by inhibiting CXCR4 or CXCL12 suppresses immune responses, indicating CREB1's role in promoting skin inflammation [1]. In non-small cell lung cancer, knockdown of CREB1 sensitizes cells to ferroptosis inducers. CREB1 transcriptionally activates stearoyl-CoA desaturase (SCD), which confers ferroptosis resistance, and high CREB1 expression is associated with poor prognosis [5]. In multiple myeloma, inhibition of CREB1 promotes anti-tumoral immunity by limiting HLA-E expression and enhancing NK cell activity [2]. In cervical cancer, depletion or inhibition of CREB1 activity reduces cell proliferation and migration, and CREB1 directly binds the viral promoter to upregulate E6/E7 oncogenes [4].

In conclusion, Creb1 is crucial in various biological processes and disease conditions. Studies using KO/CKO mouse models have revealed its significant contributions to skin inflammation, cancer development (including non-small cell lung cancer, multiple myeloma, and cervical cancer), and immune-related processes, providing insights into potential therapeutic strategies for these diseases.

References:

1. Chen, Jiaoling, Bai, Yaxing, Xue, Ke, Wang, Gang, Shao, Shuai. 2023. CREB1-driven CXCR4hi neutrophils promote skin inflammation in mouse models and human patients. In Nature communications, 14, 5894. doi:10.1038/s41467-023-41484-3. https://pubmed.ncbi.nlm.nih.gov/37736772/

2. Ismael, Aya, Robinette, Allen J, Huric, Laila, Cocucci, Emanuele, Cottini, Francesca. 2024. CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma. In Leukemia, 38, 1777-1786. doi:10.1038/s41375-024-02303-w. https://pubmed.ncbi.nlm.nih.gov/38902472/

3. Wang, Ya-Wen, Chen, Xu, Ma, Rong, Gao, Peng. 2016. Understanding the CREB1-miRNA feedback loop in human malignancies. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 8487-502. doi:10.1007/s13277-016-5050-x. https://pubmed.ncbi.nlm.nih.gov/27059735/

4. Li, Yigen, Patterson, Molly R, Morgan, Ethan L, Wang, Miao, Macdonald, Andrew. . CREB1 activation promotes human papillomavirus oncogene expression and cervical cancer cell transformation. In Journal of medical virology, 95, e29025. doi:10.1002/jmv.29025. https://pubmed.ncbi.nlm.nih.gov/37565725/

5. Shan, Guangyao, Bi, Guoshu, Zhao, Guangyin, Fan, Hong, Zhan, Cheng. 2023. Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer. In Respiratory research, 24, 277. doi:10.1186/s12931-023-02567-3. https://pubmed.ncbi.nlm.nih.gov/37957645/