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Arp2/3 complex and β1 integrin drive an invasive front through extracellular matrix adaptation in pancreatic cancer: tumor markers and signatures

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, due to its aggressive invasiveness and resistance to therapy. The dense, stiff extracellular matrix, composed primarily of collagen I and basement membrane components such as collagen IV and laminin, acts as a mechanical b...

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Main Authors: Yang, Xiufen (Author) , Qiao, Yina (Author) , Sun, Yifeng (Author) , Abdelaal, Tamer (Author) , Schuck, Kathleen (Author) , Abdelrasoul, Hend (Author) , Torre, Carolina de la (Author) , Hermes, Malte (Author) , Dong, Yan (Author) , Hu, Jingxiong (Author) , Fang, Chao (Author) , Huang, Xiaoyan (Author) , Kahlert, Christoph (Author) , Herr, Ingrid (Author) , Michalski, Christoph (Author) , Kong, Bo (Author)
Format: Article (Journal)
Language:English
Published: 1 June 2026
In: International journal of cancer
Year: 2026, Volume: 158, Issue: 11, Pages: 3038-3050
ISSN:1097-0215
DOI:10.1002/ijc.70376
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.70376
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.70376
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Author Notes:Xiufen Yang, Yina Qiao, Yifeng Sun, Tamer Abdelaal, Kathleen Schuck, Hend Abdelrasoul, Carolina De La Torre, Malte Hermes, Yan Dong, Jingxiong Hu, Chao Fang, Xiaoyan Huang, Christoph Kahlert, Ingrid Herr, Christoph W. Michalski, Bo Kong
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Summary:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, due to its aggressive invasiveness and resistance to therapy. The dense, stiff extracellular matrix, composed primarily of collagen I and basement membrane components such as collagen IV and laminin, acts as a mechanical barrier that constrains PDAC invasion. We investigated whether the actin-related protein (Arp) 2/3 complex, a key actin nucleator, is essential for PDAC cells to overcome extracellular matrix stiffness and facilitate migration. CRISPR/Cas9 knockout of the Arpc4 gene in murine PDAC cell lines derived from KrasG12D-driven transgenic mice resulted in substantially downregulated all Arp2/3 complex members. Inactivation of Arp2/3 significantly impaired PDAC cell migration, disrupted branched tubular structure formation in collagen I, and inhibited invasive front formation in organoid culture together with tumor-associated macrophages and fibroblasts. Mechanistically, β1 integrin signaling emerged as a key regulator of Arp2/3-dependent migration through collagen-rich matrices. Clinically, elevated expression of Arp2/3 complex components correlates with poor patient survival and basal-like differentiation subtypes, underscoring its role in disease progression. This study identifies the Arp2/3 complex and β1 integrin signaling as critical mediators of PDAC invasiveness and suggests them as potential therapeutic targets for mitigating PDAC progression.
Item Description:Im Titel ist "Beta" als griechischer Buchstabe geschrieben
Gesehen am 07.04.2026
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.70376

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