Abstract
The bone morphogenic protein (BMP) antagonist Gremlin-1 is a biologically significant regulator known for its crucial role in tissue differentiation and embryonic development. Nevertheless, it has been reported that Gremlin-1 can exhibit its function through BMP dependent and independent pathways. Gremlin-1 has also been reported to be involved in organ fibrosis, which has been correlated to the development of other diseases, such as renal inflammation and diabetic nephropathy. Based on growing evidence, Gremlin-1 has recently been implicated in the initiation and progression of different types of cancers. Further, it contributes to the stemness state of cancer cells. Herein, we explore the recent findings on the role of Gremlin-1 in various cancer types, including breast, cervical, colorectal, and gastric cancers, as well as glioblastomas. Additionally, we highlighted the impact of Gremlin-1 on cellular processes and signaling pathways involved in carcinogenesis. Therefore, it was suggested that Gremlin-1 might be a promising prognostic biomarker and therapeutic target in cancers.
Highlights
The cellular pathways responsible for normal cellular growth, differentiation, and survival are aberrant in cancerous cells
The Gremlin-1/vascular endothelial growth factor receptor-2 (VEGFR2) axis is considered as a promising therapeutic target that needs to be further studied, due to the fact that the currently approved VEGFR2 inhibitors are associated with side effects, such as hypertension, hypothyroidism, and coagulation disorders [58]
This review focuses on the effect of Gremlin-1 in cancerous cells, it is important to note that it plays a role in the pathogenesis of other conditions
Summary
The cellular pathways responsible for normal cellular growth, differentiation, and survival are aberrant in cancerous cells. Cancer cells orchestrate tumor growth and invasion through interacting with surrounding stromal cells, such as fibroblasts, endothelial cells, and immune cells [8] Such interactions in the tumor microenvironment (TME) facilitate other processes, such as angiogenesis and metastasis [9]. Angiogenesis is a crucial process that paves the way for tumor growth, invasion, and metastasis that leads to the spread of malignant cells to distant organs [10]. Such complex processes are driven by several genetic and epigenetic factors [11]. We aim to shed light on the recent updates and potential role of Gremlin-1 in different types of cancer
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