2. Academic Validation
  3. CCPG1-mediated reticulophagy promotes tumorigenesis and cisplatin resistance in bladder cancer

CCPG1-mediated reticulophagy promotes tumorigenesis and cisplatin resistance in bladder cancer

  • Autophagy. 2025 Dec 26:1-17. doi: 10.1080/15548627.2025.2601865.
Yang Dong 1,  Sufang Tian 1,  Xueying Peng 1,  Ping Wang 1,  Xuehong Qian 1,  Chenxi Xie 1,  Rongfu Tu 2,  Xinghuan Wang 1 3 4,  Yixian Cui 1
Affiliations

Affiliations

  • 1 Department of Urology, Department of Pathology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
  • 2 The First Affiliated Hospital of Xi'an Jiaotong University, Center for Precision Cancer Medicine, MED-X Institute, Xi'an, Shaanxi, China.
  • 3 Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
  • 4 Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei, China.
PMID: 41361995 DOI: 10.1080/15548627.2025.2601865
Abstract

Reticulophagy, a selective macroautophagy/Autophagy process targeting endoplasmic reticulum fragments via receptors, plays a critical role in cellular homeostasis. This study reveals that CCPG1, a reticulophagy receptor, drives bladder Cancer (BLCA) tumorigenesis and confers cisplatin resistance. We observed elevated reticulophagy activity in BLCA cells compared to normal counterparts, particularly under conditions of nutrient stress. CCPG1 expression was significantly upregulated in BLCA patient samples and correlated with poor prognosis. Functional studies demonstrated that CCPG1 knockdown suppressed reticulophagy, leading to decreased cell proliferation and increased Apoptosis. Conversely, overexpression of the wild-type CCPG1, but not a MAP1LC3/LC3-binding-deficient variant, rescued reticulophagy and promoted tumor growth. Notably, we found that cisplatin treatment inhibited reticulophagy by downregulating CCPG1 expression through the ATM-CHEK2/Chk2 signaling pathway. CCPG1 knockdown synergistically enhanced cisplatin cytotoxicity to BLCA cells, while CCPG1 overexpression conferred resistance. These findings highlight CCPG1-mediated reticulophagy as a driver of BLCA progression and as a potential prognostic biomarker and therapeutic target.

Keywords

ATM; CHEK2; autophagy; biomarker; endoplasmic reticulum; receptor.

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