In recent years, the discovery of ‘tumour niche’, a microenvironment that favours tumour development has changed our perspective of cancer. This microenvironment generated by the tumour cells itself and surrounding cells is capable of providing essential elements for its growth. Consequently, the homoeostasis of the secretory pathway (SP) has become an essential player in cancer development. The SP not only promotes cellular adaptation to protein misfolding due to oncogenic transformation or challenging tumour niche but also allows tumour cells to produce specific secretomes. This impacts tumour cells in cis‐ or trans‐ as well as stromal cells in the tumour niche. In this context, the Anterior GRadient 2 (AGR2) protein has been identified as a key player. AGR2 is a protein disulphide isomerase that resides in the endoplasmic reticulum (ER) and mediates the formation of disulphide bonds, catalyses the cysteine‐based redox reactions and assists the quality control of proteins. AGR2 not only plays an essential role in the homoeostasis of the SP but also exerts pro‐oncogenic gain‐of‐function due to its reported mislocalisation in the tumour niche microenvironment. In this review, we summarise the dual role of AGR2, inside and outside the ER, on the tumour niche and its microenvironment.

中文翻译：

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蛋白质二硫化物异构酶 AGR2 在肿瘤生态位中的作用

近年来，“肿瘤生态位”这一有利于肿瘤发展的微环境的发现改变了我们对癌症的看法。这种由肿瘤细胞本身和周围细胞产生的微环境能够为其生长提供必需的元素。因此，分泌途径 (SP) 的稳态已成为癌症发展的重要参与者。由于致癌转化或挑战肿瘤生态位，SP 不仅促进细胞适应蛋白质错误折叠，而且还允许肿瘤细胞产生特定的分泌组。这会影响顺式或反式中的肿瘤细胞以及肿瘤生态位中的基质细胞。在这种情况下，Anterior GRadient 2 (AGR2) 蛋白已被确定为关键参与者。AGR2 是一种蛋白质二硫键异构酶，位于内质网 (ER) 中，介导二硫键的形成，催化基于半胱氨​​酸的氧化还原反应，并有助于蛋白质的质量控制。AGR2 不仅在 SP 的稳态中发挥重要作用，而且由于其在肿瘤生态位微环境中的错误定位而发挥促癌作用。在这篇综述中，我们总结了 AGR2 在 ER 内外对肿瘤生态位及其微环境的双重作用。