GREMLIN1（GREM1）是一类结构及功能相关的分泌的半胱氨酸结节蛋白家族成员，它们的作用是封存和抑制多功能骨形态发生蛋白（BMPs）的活性。GREM1直接结合BMP二聚体，从而阻止BMP介导的BMP I型和II型受体的激活。多个研究报告鉴定GREM1的过表达为广泛范围癌症的一个促进因素。此外，GREM1基因在罕见的常染色体显性遗传性结直肠癌中发生扩增。GREM1对BMP信号转导的抑制效应与这些促进肿瘤的效应相关，包括促进癌细胞的肿瘤干细胞状态和癌相关成纤维细胞的活化。此外，已经描述了GREM1与血管内皮生长因子受体（VEGFR）结合并信号传递，以及与表皮生长因子受体（EGFR）和成纤维细胞生长因子受体（FGFR）结合并分别在乳腺癌和前列腺癌中产生促肿瘤效应。相反，一份于2022年的报告揭示了GREM1在胰腺癌中可以促进上皮状态，从而抑制胰腺肿瘤的生长和转移。在本评论中，我们将对这些分歧发现进行回顾，并尝试阐明GREM1信号传导在癌症中的作用。 © 2023. 作者

GREMLIN1 (GREM1) is member of a family of structurally and functionally related secreted cysteine knot proteins, which act to sequester and inhibit the action of multifunctional bone morphogenetic proteins (BMPs). GREM1 binds directly to BMP dimers, thereby preventing BMP-mediated activation of BMP type I and type II receptors. Multiple reports identify the overexpression of GREM1 as a contributing factor in a broad range of cancers. Additionally, the GREM1 gene is amplified in a rare autosomal dominant inherited form of colorectal cancer. The inhibitory effects of GREM1 on BMP signaling have been linked to these tumor-promoting effects, including facilitating cancer cell stemness and the activation of cancer-associated fibroblasts. Moreover, GREM1 has been described to bind and signal to vascular endothelial growth factor receptor (VEGFR) and stimulate angiogenesis, as well as epidermal and fibroblast growth factor receptor (EGFR and FGFR) to elicit tumor-promoting effects in breast and prostate cancer, respectively. In contrast, a 2022 report revealed that GREM1 can promote an epithelial state in pancreatic cancers, thereby inhibiting pancreatic tumor growth and metastasis. In this commentary, we will review these disparate findings and attempt to provide clarity around the role of GREM1 signaling in cancer.© 2023. The Author(s).