Creb3l1-KO Mouse

CREB3L1, also known as OASIS, is an endoplasmic reticulum (ER)-resident transmembrane transcription factor belonging to the bZIP transcription factor family [2,4]. It is cleaved by regulated intramembrane proteolysis to become an active transcription factor. Physiologically, it is involved in bone morphogenesis, neurogenesis, neuroendocrine regulation, secretory cell differentiation, and angiogenesis [4]. Pathologically, it is associated with diseases like osteogenesis imperfecta, certain sarcomas, glioma, breast cancer, thyroid cancer, and tissue fibrosis [4]. It also participates in pathways such as the PERK-eIF2α-ATF4 pathway in the context of ER stress and vascular calcification [3]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable in further elucidating its functions.

In anaplastic thyroid carcinoma (ATC), CREB3L1 knockdown in ATC cells attenuated invasion, and in zebrafish and nude mouse models, loss of CREB3L1 inhibited metastasis and tumor growth. It was found that CREB3L1 maintains the CAF-like property of ATC cells by activating the extracellular matrix (ECM) signaling, remodeling the tumor stromal microenvironment, and driving ATC malignancy [1]. In breast cancer, restoring CREB3L1 expression in CREB3L1-deficient cell lines reduced cell migration, anchorage-independent growth, mammary fat pad tumor formation, and lung metastases in mouse xenograft models, indicating its role as a metastasis suppressor [6]. In odontoblast differentiation, deletion of Creb3l1 in the Wnt1+ lineage led to insufficient root elongation and dentin deposition, as CREB3L1 participates in dentinogenesis and facilitates odontoblastic differentiation [5].

In conclusion, CREB3L1 plays crucial roles in multiple physiological and pathological processes. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases such as thyroid and breast cancers, as well as in biological processes like odontoblast differentiation and dentinogenesis. Understanding CREB3L1's functions provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Pan, Zongfu, Xu, Tong, Bao, Lisha, Huang, Ping, Ge, Minghua. 2022. CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment. In Molecular cancer, 21, 190. doi:10.1186/s12943-022-01658-x. https://pubmed.ncbi.nlm.nih.gov/36192735/

2. Saito, Atsushi, Omura, Issei, Imaizumi, Kazunori. 2024. CREB3L1/OASIS: cell cycle regulator and tumor suppressor. In The FEBS journal, 291, 4853-4866. doi:10.1111/febs.17052. https://pubmed.ncbi.nlm.nih.gov/38215153/

3. Liu, Aiting, Chen, Zhenwei, Li, Xiaoxue, Shen, Jiangang, Huang, Hui. . C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway. In Cardiovascular research, 119, 2563-2578. doi:10.1093/cvr/cvad133. https://pubmed.ncbi.nlm.nih.gov/37603848/

4. Zhao, Ying, Yu, Zhou, Song, Yajuan, He, Yinbin, Hu, Sheng. 2024. The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions. In International journal of medical sciences, 21, 123-136. doi:10.7150/ijms.90189. https://pubmed.ncbi.nlm.nih.gov/38164349/

5. Li, Yuanyuan, Lin, Yuxiu, Guo, Jinqiang, Liu, Huan, Chen, Zhi. 2024. CREB3L1 deficiency impairs odontoblastic differentiation and molar dentin deposition partially through the TMEM30B. In International journal of oral science, 16, 59. doi:10.1038/s41368-024-00322-y. https://pubmed.ncbi.nlm.nih.gov/39384739/

6. Mellor, Paul, Kendall, Stephanie, Smith, Shari, Saxena, Anurag, Anderson, Deborah H. 2022. Reduced CREB3L1 expression in triple negative and luminal a breast cancer cells contributes to enhanced cell migration, anchorage-independent growth and metastasis. In PloS one, 17, e0271090. doi:10.1371/journal.pone.0271090. https://pubmed.ncbi.nlm.nih.gov/35802566/