Wbp2-KO Mouse

WBP2, or WW domain-binding protein 2, is an oncogenic transcriptional co-factor involved in multiple key signaling pathways such as ER/PR, EGFR, PI3K, Hippo, and Wnt in cancer [3]. It also functions as a molecular chaperon [1]. The Hippo signaling pathway, where WBP2 interacts with YAP and TAZ, is one of the important associated pathways, and dysregulation of these pathways can lead to cancer development [2].

In cisplatin-induced acute kidney injury (CP-AKI), WBP2, highly expressed in renal proximal tubular cells, was downregulated. WBP2 was found to decelerate ferroptosis to alleviate CP-AKI by interacting with GPX4 via its PPXY1 motif, and competing with HSC70 for binding with the KEFRQ-like motifs of GPX4, thus inhibiting chaperon-mediated autophagy of GPX4 [1]. In breast cancer, it promotes the malignant development and is involved in drug resistance mechanisms related to estrogen receptor and EGFR2 status [4]. In triple-negative breast cancer, it enhances cell migration and invasion by promoting BTRC mRNA stability to activate the NF-κB pathway [5]. In non-small cell lung cancer, it promotes cancer progression by negatively regulating the Hippo pathway through competitive binding to WWC3 with LATS1 [6]. In gastric cancer, it promotes cell migration by inactivating the Hippo pathway transducer LATS2 [7].

In conclusion, WBP2 plays diverse and crucial roles in multiple biological processes and disease conditions. Its functions in cancer development and progression, as well as in renal injury, have been revealed through various studies. Understanding the role of WBP2 in these diseases can potentially provide new therapeutic targets and strategies for treatment [1,2,3,4,5,6,7].

References:

1. Deng, Zebin, Wang, Yilong, Liu, Jiachen, Dai, Yingbo, Deng, Fei. 2023. WBP2 restrains the lysosomal degradation of GPX4 to inhibit ferroptosis in cisplatin-induced acute kidney injury. In Redox biology, 65, 102826. doi:10.1016/j.redox.2023.102826. https://pubmed.ncbi.nlm.nih.gov/37516014/

2. Lim, Yvonne Xinyi, Lin, Hexian, Seah, Sock Hong, Lim, Yoon Pin. 2021. Reciprocal Regulation of Hippo and WBP2 Signalling-Implications in Cancer Therapy. In Cells, 10, . doi:10.3390/cells10113130. https://pubmed.ncbi.nlm.nih.gov/34831354/

3. Tabatabaeian, Hossein, Rao, Angad, Ramos, Alisha, Sudol, Marius, Lim, Yoon Pin. 2020. The emerging roles of WBP2 oncogene in human cancers. In Oncogene, 39, 4621-4635. doi:10.1038/s41388-020-1318-0. https://pubmed.ncbi.nlm.nih.gov/32393834/

4. Liu, Yan, He, Enping, Zhang, Yanling, Zeng, Youqing, Leng, Ping. . WW domain binding protein 2 (WBP2) as an oncogene in breast cancer: mechanisms and therapeutic prospects-a narrative review. In Gland surgery, 11, 1984-2002. doi:10.21037/gs-22-716. https://pubmed.ncbi.nlm.nih.gov/36654949/

5. Lim, Yvonne Xinyi, Lin, Hexian, Chu, Tinghine, Lim, Yoon Pin. 2021. WBP2 promotes BTRC mRNA stability to drive migration and invasion in triple-negative breast cancer via NF-κB activation. In Molecular oncology, 16, 422-446. doi:10.1002/1878-0261.13048. https://pubmed.ncbi.nlm.nih.gov/34197030/

6. Han, Qiang, Rong, Xuezhu, Lin, Xuyong, Zhao, Huanyu, Wang, Enhua. 2021. WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression. In Cell death & disease, 12, 384. doi:10.1038/s41419-021-03600-3. https://pubmed.ncbi.nlm.nih.gov/33837178/

7. Hum, Melissa, Tan, Hock Jin, Yang, Yixuan, Teh, Ming, Lim, Yoon Pin. . WBP2 promotes gastric cancer cell migration via novel targeting of LATS2 kinase in the Hippo tumor suppressor pathway. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e21290. doi:10.1096/fj.202000393R. https://pubmed.ncbi.nlm.nih.gov/33475198/