2. Academic Validation
  3. COL1A1 promotes clear cell renal cell carcinoma progression through the Wnt/β-catenin signaling pathway

COL1A1 promotes clear cell renal cell carcinoma progression through the Wnt/β-catenin signaling pathway

  • Cell Signal. 2026 Feb:138:112259. doi: 10.1016/j.cellsig.2025.112259.
Xing Ji 1,  Yongyang Yun 2,  Zhenpeng Zhu 2,  Tianyu Wu 1,  Mingjian Ruan 1,  Yu Fan 3,  Qian Zhang 4
Affiliations

Affiliations

  • 1 Department of Urology, Peking University First Hospital, Beijing 100034, China; Institution of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, China; Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
  • 2 Department of Urology, Peking University First Hospital, Beijing 100034, China; Institution of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
  • 3 Department of Urology, Peking University First Hospital, Beijing 100034, China; Institution of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, China. Electronic address: [email protected].
  • 4 Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. Electronic address: [email protected].
PMID: 41270811 DOI: 10.1016/j.cellsig.2025.112259
Abstract

Objective: To investigate COL1A1 expression, prognostic significance, functional roles, and underlying mechanisms in clear cell renal cell carcinoma (ccRCC).

Methods: COL1A1 expression was analyzed using public databases, Western blotting, and immunohistochemistry (IHC). Functional effects were evaluated through both loss-of-function and gain-of-function assays in vitro. An in vivo xenograft model was used to assess tumor growth and confirm epithelial-mesenchymal transition (EMT) marker changes by IHC. Mechanistic investigations involved dual-rescue experiments with a Wnt/β-catenin activator and inhibitor, and functional location assays using a secretion inhibitor and recombinant protein.

Results: COL1A1 was significantly upregulated in ccRCC, and high expression independently predicted poor prognosis. Bidirectional perturbations supported an oncogenic role: knockdown inhibited, whereas overexpression enhanced, cell proliferation, migration, invasion, and EMT. In vivo, COL1A1 knockdown suppressed tumor growth and histologically reversed EMT. Mechanistically, functional location studies demonstrated that COL1A1 acts predominantly from the extracellular space to activate Wnt/β-catenin signaling. This dependency was corroborated by dual-rescue experiments, in which pathway activation restored the knockdown phenotype, whereas β-catenin inhibition abrogated the effects of COL1A1 overexpression.

Conclusion: COL1A1 is a key oncogene in ccRCC, promoting progression by activating the Wnt/β-catenin axis. COL1A1 holds potential as a prognostic biomarker and therapeutic target for ccRCC.

Keywords

COL1A1; Clear cell renal cell carcinoma; Epithelialmesenchymal transition; Prognosis; Wnt/β-catenin signaling pathway.

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