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

作者全名：Yan, Benhuang; Luo, Peng; Qiu, Heping; Wang, Jianwu; Xiong, Qin; Hu, Weiwei; Wang, Fulong; Liu, Gaoyu; Zhi, Yi; Fang, Qiang; Shi, Chunmeng; Li, Weibing

作者地址：[Yan, Benhuang; Qiu, Heping; Wang, Jianwu; Zhi, Yi; Fang, Qiang; Li, Weibing] Chongqing Med Univ, Affiliated Hosp 3, Dept Urol, Chongqing 401120, Peoples R China; [Luo, Peng; Xiong, Qin; Hu, Weiwei; Wang, Fulong; Liu, Gaoyu; Shi, Chunmeng] Army Med Univ, Mil Med Univ 3, State Key Lab Trauma & Chem Poisoning, Chongqing 400038, Peoples R China

通信作者：Li, WB (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Urol, Chongqing 401120, Peoples R China.; Shi, CM (通讯作者)，Army Med Univ, Mil Med Univ 3, State Key Lab Trauma & Chem Poisoning, Chongqing 400038, Peoples R China.

来源：PATHOLOGY RESEARCH AND PRACTICE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001248327500001

JCR分区：Q2

影响因子：2.9

年份：2024

卷号：259

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Positive cofactor 4; Bladder cancer; Stemness; Sp1; Wnt5a

摘要：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/beta-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.

基金机构：National Natural Science Foundation of China [82102341]; Outstanding Scientist Program of Chongqing Talent Plan, China [CQYC20200101159]; Natural Science Foundation of Chongqing, China [CSTB2022BSXM-JCX0034]

基金资助正文：<B>Funding information</B> This work was supported by the National Natural Science Foundation of China (82102341) , the Outstanding Scientist Program of Chongqing Talent Plan, China (CQYC20200101159) , and the Natural Science Foundation of Chongqing, China (CSTB2022BSXM-JCX0034) .