ArticleMolecular cancer research : MCR2014
Integrin α3β1 can function to promote spontaneous metastasis and lung colonization of invasive breast carcinoma.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 91 citations in OpenAlex.
- Integrin α3Cancer pathogenesis and therapy · 2026Article
- SH3BP5L triggers the RAB11A-regulated integrin recycling network implicated in breast cancer metastasis.The Journal of clinical investigation · 2026Article
- Integrative Multiscale Analysis Reveals EFNA1-Driven Immune Remodeling Promotes Colorectal Cancer Lymph Node Metastasis.Human mutation · 2026Article
- Development of a novel prognostic model based on laminin α5, associated with immune infiltration and therapeutic response in ovarian cancer utilizing online resources.European journal of medical research · 2025Article
- Functional study of laminin subunit α5 in high-grade serous ovarian cancer.Journal of ovarian research · 2025Article
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
- Lung-specific metastasis: the coevolution of tumor cells and lung microenvironment.Molecular cancer · 2025Review
- Laminin α5: a key factor in tumor metastasis.Clinical & experimental metastasis · 2025Review
- ITGA3 promotes pancreatic cancer progression through HIF1α- and c-Myc-driven glycolysis in a collagen I-dependent autocrine manner.Cancer gene therapy · 2025Article
- Article
- The epidermal integrin-mediated secretome regulates the skin microenvironment during tumorigenesis and repair.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Modified bone marrow mesenchymal stem cells derived exosomes loaded with MiRNA ameliorates non-small cell lung cancer.Journal of cellular and molecular medicine · 2024Article
- Roles for epithelial integrin α3β1 in regulation of the microenvironment during normal and pathological tissue remodeling.American journal of physiology. Cell physiology · 2024Review
- ADAMTS18 deficiency associates extracellular matrix dysfunction with a higher risk of HER2-positive mammary tumorigenesis and metastasis.Breast cancer research : BCR · 2024Article
- Critical functions of extracellular matrix in brain metastasis seeding.Cellular and molecular life sciences : CMLS · 2023Review
- Vinculin Y822 is an important determinant of ligand binding.Journal of cell science · 2023Article
- Immune determinants of the pre-metastatic niche.Cancer cell · 2023Review
- Weaving the nest: extracellular matrix roles in pre-metastatic niche formation.Frontiers in oncology · 2023Review
- Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGβ5 signaling.Acta pharmacologica Sinica · 2022Article
- Chemotherapy-Induced Changes in the Lung Microenvironment: The Role of MMP-2 in Facilitating Intravascular Arrest of Breast Cancer Cells.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledSignificant evidence implicates α3β1 integrin in promoting breast cancer tumorigenesis and metastasis-associated cell behaviors in vitro and in vivo. However, the extent to which α3β1 is actually required for breast cancer metastasis remains to be determined. We used RNA interference to silence α3 integrin expression by approximately 70% in 4T1 murine mammary carcinoma cells, a model of aggressive, metastatic breast cancer. Loss of α3 integrin reduced adhesion, spreading, and proliferation on laminin isoforms, and modestly reduced the growth of orthotopically implanted cells. However, spontaneous metastasis to lung was strikingly curtailed. Experimental lung colonization after tail vein injection revealed a similar loss of metastatic capacity for the α3-silenced (α3si) cells, suggesting that critical, α3-dependent events at the metastatic site could account for much of α3β1's contribution to metastasis in this model. Reexpressing α3 in the α3si cells reversed the loss of metastatic capacity, and silencing another target, the small GTPase RhoC, had no effect, supporting the specificity of the effect of silencing α3. Parental, α3si, and α3-rescued cells, all secreted abundant laminin α5 (LAMA5), an α3β1 integrin ligand, suggesting that loss of α3 integrin might disrupt an autocrine loop that could function to sustain metastatic growth. Analysis of human breast cancer cases revealed reduced survival in cases where α3 integrin and LAMA5 are both overexpressed. IMPLICATIONS: α3 integrin or downstream effectors may be potential therapeutic targets in disseminated breast cancers, especially when laminin α5 or other α3 integrin ligands are also over-expressed.
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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.