Agr2-flox Mouse

AGR2, or anterior gradient-2, is a 20 kDa protein crucial for oxidative protein folding in the endoplasmic reticulum [4]. It's involved in several signal transduction pathways essential for cell survival and was initially discovered in Xenopus laevis, where it contributes to embryonic development. In mammals, it has diverse functions and is associated with various biological processes and diseases [4].

In colorectal cancer (CRC), neutrophil-specific Agr2 knockout (Agr2f/f;Mrp-Cre) mice were used to study the role of tumour-associated neutrophils (TANs)-secreted AGR2. Results showed that TANs are a major source of secreted AGR2 in the CRC tumour microenvironment (TME), and TAN-secreted AGR2 promotes CRC cell migration. Neutrophils-specific ablation of Agr2 in mice ameliorated CRC liver metastases, unveiling a TAN-CRC cell crosstalk via the AGR2-CD98hc-xCT axis promoting metastasis [1]. In breast cancer, AGR2 is expressed in precancerous, primary, and metastatic tumours. lncRNA LINC02273 was found to epigenetically increase AGR2 transcription, promoting breast cancer metastasis in vitro and in vivo, and the combination of AGR2 and LINC02273 is an independent prognostic factor [2,3].

In summary, AGR2 is important for oxidative protein folding and cell survival-related signal transduction. Model-based research, especially using Agr2 knockout mouse models in CRC, has revealed its role in promoting cancer metastasis. In breast cancer, its association with lncRNA-mediated regulation and prognosis also highlights its significance in understanding cancer development and potential therapeutic targeting.