Wnt Family

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Wnt proteins are a category of secreted protein molecules that undergo glycosylation and fatty acidification modifications. These proteins play vital roles in developmental processes, including the regulation of cell fate, progenitor cell proliferation, and control of symmetric division. In mammals, Wnt comprises 19 members, such as Wnt1, Wnt2, Wnt2b, Wnt3, Wnt3a, etc. These proteins can act as secreted morphogenetic factors, taking part in cell fate determination, as well as cell proliferation and differentiation. Among them, Wnt3a and Wnt5a are widely distributed and play vital roles in regulating various cellular functions, such as proliferation, differentiation, and motility. They are considered the most representative signaling proteins of the Wnt family. Wnt signaling pathways that they mediate include the classical pathway, the planar cell polarity (PCP) pathway, and the Wnt/Ca2+ pathway.

The canonical Wnt3a pathway.Figure 1. The canonical Wnt3a pathway. (He S, et al., 2015)

The Wnt signaling pathway is a complex network of proteins acting in functions most commonly seen in embryonic development and cancer, but also involved in normal physiological processes in adult animals. Previous studies have found that activation of Wnt3a, a key signaling molecule in the Wnt/β-catenin pathway, is closely associated with lung cell carcinoma (HCC) progression, including malignant transformation of hepatocytes, metastasis, drug resistance, and hepatocellular carcinoma stem cells. Knockdown of Wnt3a in vitro inactivates the Wnt/β-catenin pathway to inhibit proliferation and colony formation, induce cell cycle arrest in HCC cells, and inhibit the growth of xenograft tumors in vivo. Wnt3a may be a potential indicator to monitor the malignant transformation of hepatocytes as well as have a promising application for targeted therapy of hepatocellular carcinoma. In addition, Wnt3a also plays a role as the most commonly used culture factor for organoid construction due to its important role in stem cell proliferation and differentiation. Currently, Wnt3a is a key component in maintaining the proliferation of Lgr5+ stem cells in intestinal epithelial cells and is essential for colon crypt culture.

Wnt5a is an important member of the atypical Wnt pathway, which regulates a variety of cellular functions and participates in numerous physiological and pathological processes, and its aberrant expression can be found in a variety of epithelial and mesenchymal tumors. It has been found that Wnt5a plays an oncogenic role in colorectal cancer, neuroblastoma, and leukemia. Wnt5a was absent or significantly reduced in dedifferentiated thyroid carcinomas, and the introduction of overexpressed Wnt5a into bladder and renal cancer cell lines reversed the malignant phenotype of the cells. Furthermore, Wnt5a downregulation was positively associated with higher tumor grade and was an independent factor for poor prognosis in different tumor subtypes. In addition, Wnt5a is a potential inflammatory factor with pro-inflammatory functions. Increased expression of Wnt5a in fibroblastic synoviocytes of rheumatoid arthritis (RA) patients suggests that Wnt5a may induce enzyme release, fibroblast proliferation, inflammation, and joint damage.

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Creative BioMart is a leading biotechnology company in the development and production of GMP proteins. We are committed to advancing scientific research in tissue and organ development by providing high-quality GMP-grade Wnt family cytokines and related customized services to our customers worldwide. If you are interested in our services or products, please contact us.

Reference

  1. He S, Lu Y, Liu X, et al. (2015). Wnt3a: functions and implications in cancer[J]. Chinese journal of cancer. 34: 1-9.
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