ArticleGenes & development2010
Raf-induced MMP9 disrupts tissue architecture of human breast cells in three-dimensional culture and is necessary for tumor growth in vivo.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Beta-blockers and glioma: a systematic review of preclinical studies and clinical results.Neurosurgical review · 2021Pooled it
- When proteases reshape barriers: Basement membrane remodelling in development, wound healing and tumour progression.The FEBS journal · 2026Review
- Myelin Formation by Oligodendrocytes Is Enhanced Through Laminin-411 and Its Derived Peptide.Glia · 2025Article
- The role of dynamic reciprocity in 3D cell migration: connecting cell and matrix mechanics to migratory plasticity.npj biological physics and mechanics · 2025Review
- Review
- Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway.Pharmaceutical biology · 2023Article
- MMP-9 reinforces radiation-induced delayed invasion and metastasis of neuroblastoma cells through second-signaling positive feedback with NFκB via both ERK and IKK activation.Cell biology and toxicology · 2023Article
- Safety and tolerability of andecaliximab as monotherapy and in combination with an anti-PD-1 antibody in Japanese patients with gastric or gastroesophageal junction adenocarcinoma: a phase 1b study.Journal for immunotherapy of cancer · 2022Article
- The gastrointestinal microbiota in colorectal cancer cell migration and invasion.Clinical & experimental metastasis · 2021Review
- Tumor reversion: a dream or a reality.Biomarker research · 2021Review
- The Role of the ECM in Lung Cancer Dormancy and Outgrowth.Frontiers in oncology · 2020Review
- Tuning Cancer Fate: Tumor Microenvironment's Role in Cancer Stem Cell Quiescence and Reawakening.Frontiers in immunology · 2020Review
- Long noncoding RNA Linc00339 promotes triple-negative breast cancer progression through miR-377-3p/HOXC6 signaling pathway.Journal of cellular physiology · 2019Article
- Prediction of sorafenib treatment-related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation.European radiology · 2019Article
- B-Raf deficiency impairs tumor initiation and progression in a murine breast cancer model.Oncogene · 2019Article
- A Functionally Robust Phenotypic Screen that Identifies Drug Resistance-associated Genes Using 3D Cell Culture.Bio-protocol · 2018Article
- Dormant tumour cells, their niches and the influence of immunity.Nature cell biology · 2018Review
- Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice.Science (New York, N.Y.) · 2018Article
- Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Fibroblasts in the Tumor Microenvironment: Shield or Spear?International journal of molecular sciences · 2018Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Organization into polarized three-dimensional structures defines whether epithelial cells are normal or malignant. In a model of morphogenesis, we show that inhibiting key signaling pathways in human breast cancer cells leads to "phenotypic reversion" of the malignant cells. Using architecture as an endpoint, we report that, in all cases, signaling through Raf/MEK/ERK disrupted tissue polarity via matrix metalloproteinase9 (MMP9) activity. Induction of Raf or activation of an engineered, functionally inducible MMP9 in nonmalignant cells led to loss of tissue polarity, and reinitiated proliferation. Conversely, inhibition of Raf or MMP9 with small molecule inhibitors or shRNAs restored the ability of cancer cells to form polarized quiescent structures. Silencing MMP9 expression also reduced tumor growth dramatically in a murine xenograft model. LC-MS/MS analysis comparing conditioned medium from nonmalignant cells with or without active MMP9 revealed laminin 111 (LM1) as an important target of MMP9. LM1 has been implicated in acinar morphogenesis; thus, its degradation by MMP9 provides a mechanism for loss of tissue polarity and reinitiation of growth associated with MMP9 activity. These findings underscore the importance of the dynamic reciprocity between the extracellular matrix integrity, tissue polarity, and Raf/MEK/ERK and MMP9 activities, providing an axis for either tissue homeostasis or malignant progression.
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What OpenQuestion holds
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.