Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells.

By Ji Cao, Yijie Wang, R. Dong, Guanyu Lin, Ning Zhang, Jing Wang, Nengming Lin, Yongchuan Gu, L. Ding, Meidan Ying and 2 more. 2015

66 citations recorded by the source corpus.

Intratumoral hypoxia occurs in many solid tumors, where it is associated with the development of metastatic character. However, the connections between these phenomena are not fully understood. In this study, we define an integrative role for the E3 ubiquitin ligase subunit WSB1. In primary osteosarcomas, increased levels of WSB1 correlated with pulmonary metastatic potential. RNAi-mediated attenuation of WSB1 or disruption of its E3 ligase activity potently suppressed tumor metastasis. Quantitative proteomic and functional analyses revealed that WSB1 ubiquitylates the Rho-binding protein RhoGDI2 and promotes its proteasomal degradation, thereby activating Rac1 to stimulate tumor cell motility and invasion. Our findings show how WSB1 regulates key steps of the metastatic cascade in hypoxia-driven osteosarcoma, and they highlight a candidate therapeutic target to potentially improve the survival of patients with metastatic disease.

Subfields: Cancer Research, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Yi Zhao
2. Zhenyu Yang
3. Runsheng Chen
4. Xiaoxi Zeng

Citations in the corpus

• AlphaFold2 and its applications in the fields of biology and medicine (2023, background): “Weng et al. 92 applied AF2 to predict the 3D structure of WSB1 (SOCS-box-containing WD-40 protein), a new potential anticancer target 93 – 95 with 3D structural information not available.”