DKK2, also known as Dickkopf associated protein 2, is a secretory protein. It is known as an inhibitor of canonical Wnt/β-catenin signaling, and this signaling is crucial for the maintenance of muscle and bone [3]. DKK2 is involved in multiple biological processes and diseases. It plays a role in the interaction between muscle and bone, and in tumor-related processes such as angiogenesis, tumor cell proliferation, migration, invasion, and immune evasion [3][2][1][4][5].

In androgen-deficient mice, orchidectomy significantly enhanced Dkk2 mRNA levels in the soleus muscles and serum Dkk2 levels. Serum Dkk2 levels were negatively related to trabecular bone mineral density, suggesting Dkk2 might be involved in androgen deficiency-induced muscle wasting and osteopenia [3].

In oral squamous cell carcinoma (OSCC), compared to normal tissues, DKK2 expression was elevated. Hypoxic conditions could promote DKK2 expression. DKK2 overexpression promoted cell proliferation, migration, and invasion of OSCC cells, while DKK2 knockdown inhibited these processes by regulating the PI3K/AKT signaling pathway [1].

In colorectal cancer, DKK2 could stimulate angiogenesis via accelerating the aerobic glycolysis of CRC cells and promoting lactate secretion. It might be a potential anti-angiogenic target [2]. Also, DKK2 blockage enhanced anti-angiogenic therapy of Kras mutated colorectal cancer by activating tumor infiltrating CD8+ T cells and reducing angiogenesis [4].

In pancreatic ductal adenocarcinoma, elevated DKK2 expression predicted poorer prognosis, and knockdown of DKK2 in PDAC cells resulted in impaired cellular migration [5].

In conclusion, DKK2 has diverse functions in biological processes such as muscle-bone interaction. In disease areas, especially in multiple cancers including OSCC, colorectal cancer, and pancreatic ductal adenocarcinoma, DKK2 plays significant roles in tumor progression, angiogenesis, and immune evasion. The study of DKK2 in mouse models helps to understand its role in these biological processes and diseases, providing potential targets for treatment.