2. Academic Validation
  3. The keratin 17/YAP/IL6 axis contributes to E-cadherin loss and aggressiveness of diffuse gastric cancer

The keratin 17/YAP/IL6 axis contributes to E-cadherin loss and aggressiveness of diffuse gastric cancer

  • Oncogene. 2022 Feb;41(6):770-781. doi: 10.1038/s41388-021-02119-3.
Mengjie Li  # 1 2 3,  Xianping Rao  # 1 2 3,  Yun Cui 1 2 3,  Lu Zhang 1 2 3,  Xiang Li 1 2 3,  Boya Wang 3 4,  Yijun Zheng 1 2 5,  Lisong Teng 2 5,  Tianhua Zhou 6 7 8 9,  Wei Zhuo 10 11 12
Affiliations

Affiliations

  • 1 Department of Cell Biology and Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Cancer Center, Zhejiang University, Hangzhou, China.
  • 3 Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
  • 4 Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 5 Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.
  • 6 Department of Cell Biology and Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. tzhou@zju.edu.cn.
  • 7 Cancer Center, Zhejiang University, Hangzhou, China. tzhou@zju.edu.cn.
  • 8 Institute of Gastroenterology, Zhejiang University, Hangzhou, China. tzhou@zju.edu.cn.
  • 9 Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. tzhou@zju.edu.cn.
  • 10 Department of Cell Biology and Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. wzhuo@zju.edu.cn.
  • 11 Cancer Center, Zhejiang University, Hangzhou, China. wzhuo@zju.edu.cn.
  • 12 Institute of Gastroenterology, Zhejiang University, Hangzhou, China. wzhuo@zju.edu.cn.
  • # Contributed equally.
PMID: 34845376 DOI: 10.1038/s41388-021-02119-3
Abstract

DGC is a particular aggressive malignancy with poor prognosis. Recent omics studies characterized DGC with CDH1/E-cadherin loss and EMT-signatures. However, the underlying mechanisms for maintaining the aggressive behavior and molecular features of DGC remain unclear. Here, we find that intermediate filaments KRT17 is significantly lower in DGC tissues than that in intestinal gastric Cancer tissues and associated with poor prognosis of DGC. We demonstrate that downregulation of KRT17 induces E-cadherin loss, EMT changes, and metastasis behaviors of GC cells. Mechanistically, the loss of intermediate filaments KRT17 induces reorganization of Cytoskeleton, further activates YAP signaling, and increases IL6 expression, which contributes to the enhanced metastasis ability of GC cells. Together, these results indicate that KRT17/YAP/IL6 axis contributes to maintaining E-cadherin loss, EMT feature, and metastasis of DGC, providing a new insight into the role of aberrant intermediate filaments in DGC malignancy.

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