1新光醫院 泌尿科,2轉譯醫學中心;3台北醫學大學 醫學院;4輔仁大學 醫學院

UBE2C functions as a potential oncogene by promoting bladder tumor progression and lymphatic metastasis

Kuang-Yu Chou1, Thomas I-Sheng Hwang1,3,4, Te-Fu Tsai1, Chao-Yen Ho1, and An-Chen Chang2

Department of Urology1 and Translational Medicine Center2, Shin Kong Wu Ho-Su Memorial Hospital; Department of Urology, Taipei Medical University3; Division of Urology, School of Medicine, Fu-Jen Catholic University4, Taipei, Taiwan.


Bladder cancer (BC) is a common urological malignancy worldwide. Vasculogenic mimicry (VM), a new type of tumor angiogenesis organized by cancer cells, is conducive to increasing cell differentiation, invasiveness and tumor growth. However, the mechanisms of VM formation in BC have not been adequately explored. Ubiquitin-conjugating enzyme 2C (UBE2C) acts as a proto-oncogene and has been implicated in the carcinogenesis of various human tumors. In present project, we aim to explore whether UBE2C promotes VM formation, which leads to lymphatic metastasis of BC.

Materials and Methods:

Analyze the cell mobility of BC by using wound healing and transwell migration assay. Western blot and qPCR are used to explore indicated proteins and mRNAs expression, respectively. Tube formation assay is an in vitro model for detecting angiogenesis. Immunohistochemistry staining is used to measure the levels of indicated proteins expression in tissues; Finally, animal experiments are used to analyze the malignant progression and distant metastasis of bladder cancer regulated by VM.


Based on the results of TCGA database, higher UBE2C expression was observed in the BC tissues when compared with that noted in the normal tissue. UBE2C levels were also significantly associated with clinical grading, tumor progression and lymph node metastasis in human BC. From in vitro analysis, knockdown of UBE2C prevented VM formation in BC via suppressing epithelial–mesenchymal transition. We also found that UBE2C blockade impeded cell migration and invasion abilities. The conditioned medium from UBE2C shRNA-treated BC cells reduced lymphangiogenesis of human lymphatic endothelial cells (HLEC). In a popliteal LN metastasis mouse model of BC, UBE2C blockade inhibited tumor growth and lymphatic metastasis in vivo.  


Our findings offer important insights into how UBE2C facilitates malignant progression and lymphatic metastasis in BC. Targeting UBE2C is expected to develop into a new strategy for the BC treatment.

    2023-01-02 23:47:03
    2023-01-02 23:48:17
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