2. Academic Validation
  3. PC4 promotes bladder cancer progression and stemness by directly interacting with Sp1 to transcriptionally activate the Wnt5a/β-catenin pathway

PC4 promotes bladder cancer progression and stemness by directly interacting with Sp1 to transcriptionally activate the Wnt5a/β-catenin pathway

  • Pathol Res Pract. 2024 Jul:259:155369. doi: 10.1016/j.prp.2024.155369.
Benhuang Yan 1,  Peng Luo 2,  Heping Qiu 1,  Jianwu Wang 1,  Qin Xiong 2,  Weiwei Hu 2,  Fulong Wang 2,  Gaoyu Liu 2,  Yi Zhi 1,  Qiang Fang 1,  Chunmeng Shi 3,  Weibing Li 4
Affiliations

Affiliations

  • 1 Department of Urology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
  • 2 State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China.
  • 3 State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China. Electronic address: shicm@sina.com.
  • 4 Department of Urology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China. Electronic address: liweibing63@cqmu.edu.cn.
PMID: 38820928 DOI: 10.1016/j.prp.2024.155369
Abstract

Bladder Cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder Cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder Cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder Cancer cell proliferation and metastasis by reducing the expression of genes related to Cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/β-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in Cancer stemness regulation and provides a promising strategy for bladder Cancer therapy.

Keywords

Bladder cancer; Positive cofactor 4; Sp1; Stemness; Wnt5a.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P1416A
    99.02%, WNT5A Agonist
    Wnt