ArticleBioscience reports2018
Integrin αvβ6 plays a bi-directional regulation role between colon cancer cells and cancer-associated fibroblasts.
Article in Bioscience reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 50 citations in OpenAlex.
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- The CXCL12-CXCR4 axis in colorectal cancer: immune regulation, metastatic progression, and therapeutic implications.Frontiers in immunology · 2026Review
- Integrin signaling in tumor biology: mechanisms of intercellular crosstalk and emerging targeted therapies.PeerJ · 2025Review
- TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Targeting of 3D oral cancer spheroids by αVβ6 integrin using near-infrared peptide-conjugated IRDye 680.Cancer cell international · 2024Article
- Biophysical perspectives to understanding cancer-associated fibroblasts.APL bioengineering · 2024Review
- Modulating extracellular matrix stiffness: a strategic approach to boost cancer immunotherapy.Cell death & disease · 2024Review
- Integrinβ-1 in disorders and cancers: molecular mechanisms and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool.Journal of biomedical science · 2024Review
- Cross-Talk between the TGF-β and Cell Adhesion Signaling Pathways in Cancer.International journal of medical sciences · 2024Review
- Insights into the Tumor Microenvironment-Components, Functions and Therapeutics.International journal of molecular sciences · 2023Review
- Review
- Overcoming the Fibrotic Fortress in Pancreatic Ductal Adenocarcinoma: Challenges and Opportunities.Cancers · 2023Review
- Preclinical Evaluation ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
- Review
- Intimate communications within the tumor microenvironment: stromal factors function as an orchestra.Journal of biomedical science · 2023Review
- Role and mechanism of fibroblast-activated protein-α expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis.Frontiers in immunology · 2023Review
- Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.Cancer communications (London, England) · 2023Review
- TGF-β Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development.International journal of molecular sciences · 2022Review
- Cancer-Associated Fibroblasts: The Origin, Biological Characteristics and Role in Cancer-A Glance on Colorectal Cancer.Cancers · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor microenvironment (TME) is the cellular environment in which tumor exists, and it contributes to tumor formation and progression. The TME is composed of tumor cells, stromal cells, cytokines, and chemotactic factors of which fibroblasts are the main cellular components. In our present study, we found that colorectal cancer (CRC) cells expressing integrin αvβ6 clearly could induce morphological changes in inactive fibroblasts and increased the expression of activated fibroblast markers such as α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Those activated fibroblasts in the TME are called cancer-associated fibroblasts (CAFs). In order to investigate the mechanism by which CRC cells expressing integrin αvβ6 activated CAFs, a series of assays have been carried out in the follow-up. We found that CRC cells could secrete inactive transforming growth factor β (TGF-β); however, integrin αvβ6 activated TGF-β, which subsequently activated fibroblasts. This process was disrupted by knockdown of integrin αvβ6. In contrast, activated fibroblasts could promote CRC cell invasion. In particular, the strengthening effect on expression of integrin αvβ6 in colon cancer cells was obvious. Additionally, we found that CAFs could secrete stromal cell-derived factor-1 (SDF-1) and promote CRC cell metastasis in distant organs via the SDF-1/C-X-C chemokine receptor type 4 (CXCR4) axis. Taken together, we assumed that CRC cells and CAFs activated one another and worked together to promote cancer progression, with integrin αvβ6 playing a role in the bi-directional regulation of these cells. Hence, integrin αvβ6 may serve as a therapeutic target for the future CRC treatment.
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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.