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Cell Biology of Cancer Invasion: 2nd Edition

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Metastasis".

Deadline for manuscript submissions: 15 January 2026 | Viewed by 2113

Special Issue Editor


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Guest Editor
Sasaki Institute, Tokyo, Japan
Interests: invadopodia; cell biology; cancer biology; cell culture; cell signaling; apoptosis; cell proliferation; western blot analysis; immunohistochemistry; flow cytometry; molecular cell biology
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Special Issue Information

Dear Colleagues,

The invasion of tumor cells is a prerequisite for metastasis, the most dreadful aspect of cancer. Cancer cells detach from the primary tumor and migrate through the tumor stroma to reach blood vessels, where they intravasate into the bloodstream. After cancer cells arrive at the distant organ, they extravasate and colonize to form secondary tumors. A dense extracellular matrix that acts as a physical barrier exists within the basement membrane, tumor stroma, and blood vessel walls. Therefore, the invasive activity of tumor cells, i.e., degradation of the extracellular matrix and coordinated migration, is necessary for cancer metastasis.

The acquisition of invasive phenotypes is induced by the activation of oncogenic signaling pathways and epithelial–mesenchymal transition. The invasion of tumor cells is mediated by the formation of cellular structures called invadopodia, dynamic reorganization of the cytoskeleton, secretion and focalization of matrix metalloproteinases, and remodeling of the extracellular matrix. Moreover, tumor microenvironments, such as fibrotic stroma and tumor stromal cells, including cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM), are known to promote the invasion of tumor cells. Recent advances including genome sequencing, multi-omics analyses, gene-editing technology, and state-of-the-art microscopies have provided new insights into the mechanisms of cancer invasion.

This Special Issue invites original research articles and reviews that are related to cell biological aspects of cancer invasion, such as the topics described above.

We look forward to receiving your contributions.

Dr. Hideki Yamaguchi
Guest Editor

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Keywords

  • invasion
  • metastasis
  • intravasation
  • extravasation
  • invadopodia
  • tumor microenvironment
  • epithelial–mesenchymal transition
  • cell migration
  • cytoskeleton
  • cell adhesion
  • extracellular matrix
  • matrix metalloprotease
  • cancer-associated fibroblast
  • tumor-associated macrophage

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Published Papers (2 papers)

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Research

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17 pages, 9739 KB  
Article
TCN1 Drives Malignant Progression of Pancreatic Cancer Through STAT4-Mediated Transcriptional Activation of the DUOX2/ROS Signaling Axis
by Zonglin Liu, Dongxue Ju, Ze Yu, Binru Zhang, Dongbo Xue and Yongwei Wang
Cancers 2025, 17(20), 3300; https://doi.org/10.3390/cancers17203300 - 12 Oct 2025
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Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its aggressive clinical behavior and intricate microenvironment regulation, leading to dismal prognosis. Elucidating the molecular mechanisms underlying PDAC pathogenesis is crucial for developing improved therapeutic approaches. The functional significance and molecular basis of transcobalamin 1 [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its aggressive clinical behavior and intricate microenvironment regulation, leading to dismal prognosis. Elucidating the molecular mechanisms underlying PDAC pathogenesis is crucial for developing improved therapeutic approaches. The functional significance and molecular basis of transcobalamin 1 (TCN1) in PDAC remain largely unexplored. Methods and Results: Through integrated analysis of TCGA and GTEx datasets combined with 80 clinical specimens, we identified significant TCN1 overexpression in PDAC, showing a positive association with tumor stage and negative associations with histological differentiation and overall survival. Functional investigations showed that TCN1 enhanced pancreatic cancer cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in both in vitro and in vivo models. Mechanistically, TCN1 physically interacts with signal transducer and activator of transcription 4 (STAT4) to enhance its transcriptional activity. Chromatin immunoprecipitation (ChIP) assays showed that STAT4-mediated transcriptional activation of dual oxidase 2 (DUOX2) occurs through direct promoter binding. As a pivotal reactive oxygen species (ROS)-generating enzyme, DUOX2 overexpression elevates intracellular ROS levels, thereby promoting EMT progression and activating proliferation-related signaling cascades. Antioxidant treatment effectively abrogated TCN1-driven oncogenic phenotypes, establishing ROS as the critical downstream mediator. Conclusions: Collectively, our findings reveal a novel TCN1/STAT4/DUOX2 regulatory axis that exacerbates PDAC progression by remodeling redox homeostasis. This signaling cascade may serve as a prognostic biomarker and a potential therapeutic target for ROS-directed precision therapy in PDAC. Full article
(This article belongs to the Special Issue Cell Biology of Cancer Invasion: 2nd Edition)
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Review

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34 pages, 1483 KB  
Review
Choice of Animal Models to Investigate Cell Migration and Invasion in Glioblastoma
by Piyanka Hettiarachchi and Taeju Park
Cancers 2025, 17(17), 2776; https://doi.org/10.3390/cancers17172776 - 26 Aug 2025
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Abstract
Glioblastoma is an aggressive and prevalent form of brain cancer characterized by rapid tumor cell migration and invasion into surrounding healthy tissues, making it resistant to conventional treatments. Despite advances in therapeutic approaches, patient prognosis remains poor, with a median survival of approximately [...] Read more.
Glioblastoma is an aggressive and prevalent form of brain cancer characterized by rapid tumor cell migration and invasion into surrounding healthy tissues, making it resistant to conventional treatments. Despite advances in therapeutic approaches, patient prognosis remains poor, with a median survival of approximately 15 months. Tumor cell infiltration along perivascular spaces and white matter tracts is a major driver of recurrence, underscoring the need for experimental models that accurately capture these invasive behaviors. Animal models remain indispensable for this purpose, offering insights that cannot be fully replicated in vitro. This review focuses on applying animal models to elucidate the mechanisms underlying glioblastoma cell migration and invasion, which remain critical to improving therapeutic outcomes. By comparing the advantages of animal models with in vitro systems, we highlight the unique insights animal models provide, particularly in capturing the intricate dynamics of tumor cell motility. In particular, patient-derived xenograft (PDX) models preserve patient-specific heterogeneity and invasion patterns, such as white matter tract and perivascular infiltration, enabling clinically relevant drug testing. Zebrafish xenografts provide real-time, high-resolution visualization of tumor-vascular interactions, facilitating rapid assessment of invasion dynamics and early-stage drug screening. Genetically engineered models (GEM) allow precise discrimination of how defined genetic alterations drive specific invasive routes in the brain. Furthermore, we explore the use of advanced imaging techniques in these models to monitor tumor progression in real time. Moreover, we discuss the major drawbacks of these animal models, such as incomplete immune components and tumor microenvironment recapitulation. Ultimately, animal models are essential for bridging the gap between basic research and clinical application, offering a powerful platform for developing targeted strategies to combat glioblastoma’s relentless progression. Full article
(This article belongs to the Special Issue Cell Biology of Cancer Invasion: 2nd Edition)
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