2. Academic Validation
  3. DSG2 promotes pancreatic cancer stem cell maintenance via support of tumour and macrophage cellular cross-talk

DSG2 promotes pancreatic cancer stem cell maintenance via support of tumour and macrophage cellular cross-talk

  • Cell Death Dis. 2025 Jul 4;16(1):492. doi: 10.1038/s41419-025-07833-4.
Faming Wang 1 2,  Tao Sun 3,  Ning Wang 1 2,  Wei Wei 1 2,  Ying Mei 1,  Qiang Yan 4 5 6 7
Affiliations

Affiliations

  • 1 The Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, Zhejiang, China.
  • 2 Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China.
  • 3 Clinical Laboratory, The Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, Zhejiang, PR China.
  • 4 Department of Hepatobiliary and Pancreatic Surgery, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou Central Hospital, Huzhou, China. 13609849612@163.com.
  • 5 Department of Surgery, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. 13609849612@163.com.
  • 6 Department of Surgery, Affiliated Central Hospital of Huzhou University, Huzhou, China. 13609849612@163.com.
  • 7 Huzhou Key Laboratory of intelligent and digital precision Surgery, Huzhou, China. 13609849612@163.com.
PMID: 40615400 DOI: 10.1038/s41419-025-07833-4
Abstract

Pancreatic Cancer Stem Cells (PCSCs) are a small population of cells in tumours that exhibit enhanced self-renewal and differentiation capabilities. CSCs proactively remodel the tumour microenvironment to maintain CSC stemness, which contributes to chemotherapy resistance. Compared with targeting PCSCs themselves, targeting the PCSC niche may be a novel strategy for pancreatic Cancer (PC) therapy. Here, we found that DSG2, a member of the desmosomal Cadherin family, is highly expressed in PCSCs. DSG2 upregulation is correlated with adverse outcomes in PC patients. DSG2 knockdown suppressed IL-4 and GM-CSF expression, which promoted the enrichment of tumour-associated macrophages to establish a supportive PCSC niche. Furthermore, we found that the IL-8/CXCR2 axis interacts with DSG2 to promote PCSC stemness and gemcitabine resistance by activating the Wnt/β-catenin pathway. These findings highlight the novel regulatory mechanism of DSG2 in PC, providing new targets for the development of therapeutics targeting PCSC niches.

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