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Figure S5 from Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells

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posted on 2023-03-31, 00:11 authored by Ji Cao, Yijie Wang, Rong Dong, Guanyu Lin, Ning Zhang, Jing Wang, Nengming Lin, Yongchuan Gu, Ling Ding, Meidan Ying, Qiaojun He, Bo Yang

(A) Correlation between RhoGDI2 expression levels and metastatic potential in osteosarcoma patients. (B) Cells were exposed to hypoxia for 24 h or cells infected with control lentivirus (pCCL) and lentivirus-WSB1. RhoGDI2 mRNA expression was analyzed by RT-PCR and shown as a histogram after normalization, β-Actin was used as a control gene. (C) KHOS/NP cells treated with hypoxia for 24h together with 10 μM MG132, and RhoGDI2 protein levels were measured by western-blot analysis. (D) Colocalization of endogenous WSB1 and RhoGDI2. KHOS/NP cells were subjected to immunofluorescence staining with anti-WSB1 and anti-RhoGDI2 antibodies.

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ARTICLE ABSTRACT

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. Cancer Res; 75(22); 4839–51. ©2015 AACR.

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