2. Academic Validation
  3. Matrix stiffness maintains bladder cancer stemness via integrin-nuclear skeleton axis

Matrix stiffness maintains bladder cancer stemness via integrin-nuclear skeleton axis

  • Cell Death Dis. 2025 Dec 12;16(1):887. doi: 10.1038/s41419-025-08222-7.
Yiran Tao # 1 2,  Jiayu Huang # 1 2 3,  Jianfeng Hou # 4,  Zhuoer Hu # 5 6,  Tianyou Zhang 1 2,  Zijun Mo 1 2,  Kaixuan Zeng 7,  Jialin Wu 1 2,  Dejuan Wang 8 9,  Jianguang Qiu 10 11
Affiliations

Affiliations

  • 1 Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 2 Biomedical lnnovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 3 Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
  • 4 Department of Orthopedic Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
  • 5 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 6 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 7 School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, China.
  • 8 Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. [email protected].
  • 9 Biomedical lnnovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. [email protected].
  • 10 Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. [email protected].
  • 11 Biomedical lnnovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 41387479 DOI: 10.1038/s41419-025-08222-7
Abstract

Tumors have a unique niche system that plays an important role in their occurrence and development. At present, there is increasing interest in the biomechanical properties of niches. The increased stemness of Cancer cells is closely related to bladder Cancer progression and recurrence. However, how biomechanical properties in the niche regulate bladder Cancer stemness remains unclear. Here, we show that as bladder Cancer progresses, matrix stiffness increases, and tumor stemness increases. Mechanistically, high matrix stiffness mediates β-catenin nuclear translocation by increasing the nuclear pore size. On the Other hand, it promotes the expression of the nuclear cytoskeletal protein Lamin A/C, inhibits the nuclear export of β-catenin, and finally, it upregulates the Wnt pathway to increase the stemness of Cancer cells. These findings reveal a role for matrix stiffness in the regulation of stemness in bladder Cancer cells and suggest that targeting matrix stiffness may be an effective strategy to delay bladder Cancer progression.

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