Wnt5b-KO Mouse

Wnt5b, a member of the WNT family closely related to WNT5A, is crucial for cell migration, proliferation, and differentiation in many cell types. It signals through the non-canonical β-catenin-independent signaling pathway and often acts as an antagonist of canonical WNT signaling [1]. Wnt5b is involved in various developmental pathways, both in normal and pathological physiology [2].

In osteosarcoma, Wnt5B is highly expressed in tumors, correlating with metastasis, histologic subtype, and reduced survival. In osteosarcoma cell lines and patient-derived spheres, it promotes cancer stem-like cell properties such as sphere size, formation efficiency, cell proliferation, migration, and chemoresistance to methotrexate. In vivo, it increases lung and liver metastasis [3].

In non-small cell lung cancer (NSCLC), Wnt5B overexpression in specimens correlates with advanced TNM stage, lymph node metastasis, and poor prognosis. It promotes the malignant phenotype of NSCLC cells through the FZD3-DVL3-RAC1-PCP-JNK pathway [4].

In Pacific white shrimp, Wnt5b expression is regulated by the IMD-Relish and JAK-STAT pathways, and silencing it increases the expression of some antimicrobial peptides, suggesting it plays a negative role in antibacterial response [5].

In bone cancer pain, the protein expression of Wnt5b and its receptor Ryk is upregulated in ipsilateral DRGs of tumor-bearing mice. Wnt5b/Ryk promotes the trafficking of P2X3 receptors to the membrane via CaMKII activation, leading to peripheral sensitization and pain [6].

In conclusion, Wnt5b is essential for multiple cellular processes and is implicated in various disease conditions. Its role in diseases like osteosarcoma, NSCLC, antibacterial response in shrimp, and bone cancer pain has been revealed through in vivo studies, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Suthon, Sarocha, Perkins, Rachel S, Bryja, Vitezslav, Miranda-Carboni, Gustavo A, Krum, Susan A. 2021. WNT5B in Physiology and Disease. In Frontiers in cell and developmental biology, 9, 667581. doi:10.3389/fcell.2021.667581. https://pubmed.ncbi.nlm.nih.gov/34017835/

2. Perkins, Rachel S, Suthon, Sarocha, Miranda-Carboni, Gustavo A, Krum, Susan A. 2021. WNT5B in cellular signaling pathways. In Seminars in cell & developmental biology, 125, 11-16. doi:10.1016/j.semcdb.2021.09.019. https://pubmed.ncbi.nlm.nih.gov/34635443/

3. Perkins, Rachel S, Murray, Glenn, Suthon, Sarocha, Miranda-Carboni, Gustavo A, Krum, Susan A. . WNT5B drives osteosarcoma stemness, chemoresistance and metastasis. In Clinical and translational medicine, 14, e1670. doi:10.1002/ctm2.1670. https://pubmed.ncbi.nlm.nih.gov/38689429/

4. Zhao, Huanyu, Wu, Guangping, Luo, Yuan, Li, Qingchang, Wang, Enhua. 2024. WNT5B promotes the malignant phenotype of non-small cell lung cancer via the FZD3-DVL3-RAC1-PCP-JNK pathway. In Cellular signalling, 122, 111330. doi:10.1016/j.cellsig.2024.111330. https://pubmed.ncbi.nlm.nih.gov/39094673/

5. Yang, Linwei, Wang, Zi-Ang, Zuo, Hongliang, He, Jianguo, Xu, Xiaopeng. 2022. Wnt5b plays a negative role in antibacterial response in Pacific white shrimp Penaeus vannamei. In Developmental and comparative immunology, 133, 104411. doi:10.1016/j.dci.2022.104411. https://pubmed.ncbi.nlm.nih.gov/35447159/

6. He, Jin-Jin, Wang, Xiao, Liang, Chao, Yang, Ruo-Han, Fang, Dong. 2020. Wnt5b/Ryk-mediated membrane trafficking of P2X3 receptors contributes to bone cancer pain. In Experimental neurology, 334, 113482. doi:10.1016/j.expneurol.2020.113482. https://pubmed.ncbi.nlm.nih.gov/32979370/