Targeting Ube2c Reduces Vasculogenic Mimicry-Mediated Malignant Progression and Lymphatic Metastasis in Bladder Tumor

Project: A - Government Institutionb - National Science and Technology Council

Project Details

Description

Bladder cancer, the second most common urinary tract tumor after prostate cancer, exhibits a recurrence rate of up to 70% following treatment. Recurrent bladder cancer often progresses to an invasive form with high invasion and metastatic capabilities. Lymph nodes are common sites of metastasis in bladder cancer, and patients with lymph node involvement generally have a poor prognosis. However, the mechanisms underlying lymphatic metastasis in bladder cancer remain poorly understood. In this study, we aimed to investigate the role of UBE2C in regulating the invasiveness and lymphatic metastasis of bladder cancer and to elucidate the underlying molecular mechanisms. Initially, analysis of the TCGA-BLCA database revealed a positive correlation between UBE2C expression and bladder tumor malignancy, lymphatic metastasis, and tumor progression. Further cell experiments demonstrated that UBE2C enhances cancer cell invasiveness and vasculogenic mimicry (VM) formation, a process involving the transformation of cancer cells into vascular-like structures, by regulating the epithelial-mesenchymal transition transcription factor TWIST1. Targeting UBE2C significantly reduced bladder cancer cell invasiveness and VM formation. Conversely, overexpression of UBE2C strengthened the malignancy of bladder cancer cells. GSEA analysis indicated the involvement of the AKT/FOXO1 signaling pathway in UBE2C-mediated regulation of bladder cancer cell invasiveness and VM formation. Additionally, this study found that UBE2C, in collaboration with CCL2, regulates the infiltration of lymphatic endothelial cells into the bladder tumor microenvironment, leading to lymphangiogenesis. Finally, experiments using popliteal lymph node animal models demonstrated that targeting UBE2C reduces bladder tumor size and lymphatic metastasis.
StatusFinished
Effective start/end date8/1/217/31/23

Keywords

  • Bladder cancer
  • UBE2C
  • EMT
  • Invasiveness
  • Vasculogenic mimicry
  • Lymphatic metastasisBladder cancer, UBE2C, EMT, Invasiveness, VasculogenicLymphatic metastasis

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