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 proteolytically activated through regulated intramembrane proteolysis (RIP) and plays diverse roles in physiological processes such as bone morphogenesis, neurogenesis, neuroendocrine regulation, secretory cell differentiation, and angiogenesis [4]. Pathologically, it is implicated in various conditions including osteogenesis imperfecta, fibro myxoid sarcoma, glioma, breast cancer, thyroid cancer, and tissue fibrosis [4]. It is also involved in pathways like the PERK-eIF2α-ATF4 pathway during endoplasmic reticulum stress [3].

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 maintained the CAF-like property of ATC cells by activating the ECM signaling, remodeling the tumor stromal microenvironment and driving ATC malignancy [1]. In triple negative and luminal A breast cancer cells, reduced Creb3l1 expression contributed to enhanced cell migration, anchorage-independent growth and metastasis. Restoration of Creb3l1 expression in HCC1806 cells reduced mammary fat pad tumor formation and lung metastases in mouse xenograft models [6]. In odontoblastic differentiation, deletion of Creb3l1 in the Wnt1+ lineage led to insufficient root elongation and dentin deposition in mice [5].

In conclusion, Creb3l1 plays essential roles in multiple biological processes and disease conditions. Gene knockout or knockdown models in vivo, such as in mouse models for thyroid cancer, breast cancer, and odontoblastic differentiation, have significantly contributed to understanding its functions. These models have revealed its role in tumor growth, metastasis, and cell differentiation, providing insights into potential therapeutic targets for related diseases.