ArticleOncogene2014
Dual roles of hemidesmosomal proteins in the pancreatic epithelium: the phosphoinositide 3-kinase decides.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Morphological abnormalities in the ureter of type XVII collagen-deficient mice.Scientific reports · 2026Article
- Polarity of hemidesmosome instructive light-curable biosealants guides nascent extracellular matrix for favorable epithelial interactions.Materials today. Bio · 2025Article
- Mechanical Stretch-Induced Interlayer Coordination between MMP2 and COL17A1 Exacerbates Regenerative Exhaustion in Skin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unveiling Collagen's Role in Breast Cancer: Insights into Expression Patterns, Functions and Clinical Implications.International journal of general medicine · 2024Review
- G protein-coupled estrogen receptor 1 and collagen XVII endodomain expression in human cutaneous melanomas: can they serve as prognostic factors?Pathology oncology research : POR · 2024Article
- Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment.Cancer science · 2023Article
- Article
- Sialyl LewisCancers · 2023Article
- Junctional epithelium and hemidesmosomes: Tape and rivets for solving the "percutaneous device dilemma" in dental and other permanent implants.Bioactive materials · 2022Review
- The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes?Journal of experimental & clinical cancer research : CR · 2022Review
- Tapping basement membrane motifs: Oral junctional epithelium for surface-mediated soft tissue attachment to prevent failure of percutaneous devices.Acta biomaterialia · 2022Article
- Targeting the stem cell niche: role of collagen XVII in skin aging and wound repair.Theranostics · 2022Review
- BP180/Collagen XVII: A Molecular View.International journal of molecular sciences · 2021Review
- EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis.The Journal of cell biology · 2021Article
- S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives.Frontiers in oncology · 2021Review
- High Expression of COL17A1 Predicts Poor Prognosis and Promotes the Tumor Progression via NF-Journal of oncology · 2020Article
- The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond.Frontiers in oncology · 2020Review
- Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments.Cancers · 2019Review
- Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer.Cancers · 2019Review
- Ping-Pong-Tumor and Host in Pancreatic Cancer Progression.Frontiers in oncology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Given the failure of chemo- and biotherapies to fight advanced pancreatic cancer, one major challenge is to identify critical events that initiate invasion. One priming step in epithelia carcinogenesis is the disruption of epithelial cell anchorage to the basement membrane which can be provided by hemidesmosomes (HDs). However, the existence of HDs in pancreatic ductal epithelium and their role in carcinogenesis remain unexplored. HDs have been explored in normal and cancer pancreatic cells, and patient samples. Unique cancer cell models where HD assembly can be pharmacologically manipulated by somatostatin/sst2 signaling have been then used to investigate the role and molecular mechanisms of dynamic HD during pancreatic carcinogenesis. We surprisingly report the presence of mature type-1 HDs comprising the integrin α6β4 and bullous pemphigoid antigen BP180 in the human pancreatic ductal epithelium. Importantly, HDs are shown to disassemble during pancreatic carcinogenesis. HD breakdown requires phosphoinositide 3-kinase (PI3K)-dependent induction of the matrix-metalloprotease MMP-9, which cleaves BP180. Consequently, integrin α6β4 delocalizes to the cell-leading edges where it paradoxically promotes cell migration and invasion through S100A4 activation. As S100A4 in turn stimulates MMP-9 expression, a vicious cycle maintains BP180 cleavage. Inactivation of this PI3K-MMP-9-S100A4 signaling loop conversely blocks BP180 cleavage, induces HD reassembly and inhibits cell invasion. We conclude that mature type-1 HDs are critical anchoring structures for the pancreatic ductal epithelium whose disruption, upon PI3K activation during carcinogenesis, provokes pancreatic cancer cell migration and invasion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.