• Targeting β1-integrin, an effective approach against metastatic cancer cells
  • Hanieh Khoubanfar,1 Shahin Gharedaghi,2 Fatemeh B. Rassouli,3,*
    1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
    2. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
    3. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran, - Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University


  • Introduction: Integrins are a family of αβ heterodimeric transmembrane proteins that mediate attachment of cells to the extracellular matrix and thus, regulate cell adhesion, motility, and proliferation. These ubiquitously expressed cell surface receptors bind to extracellular ligands such as fibronectin, collagen and laminins that eventually lead to recruitment of kinases and activation of downstream signalling pathways. β1-integrin, also known as CD29, is overexpressed in many human cancers, and involved in anchorage-independent survival and metastasis of malignant cells. Since high mortality rate of cancer is mainly due to re-emergence of cancer cells and their migration from primary sites to distant locations, targeting metastasis mediators such as β1-integrin would improve therapeutic outcomes.
  • Methods: : A systematic search was performed in databases Science Direct, PubMed, Wiley Online Library and Google Scholar, using key words cancer cell metastasis, β1-integrin, CD29 and targeted therapy.
  • Results: A number of in vitro and in vivo studies have reported effective targeting of β1-integrin by antibodies, short hairpin RNA and small molecules such as 2,2'-(methylimino) di (8-quinolinol) that inhibited metastatic growth of cancer cells. In addition, β1-integrin inhibitors have been or are being evaluated in clinical trials including ATN-161, a peptide derived from the sequence of fibronectin that act as an antagonist, volociximab, a humanized monoclonal antibody, and JSM6427, is a highly selective small-molecule. Overall, current studies indicated the importance of targeting β1-integrin as a new paradigm for metastasis prevention, and revealed its therapeutic advantage in treatment of patients with aggressive cancers.
  • Conclusion: A number of in vitro and in vivo studies have reported effective targeting of β1-integrin by antibodies, short hairpin RNA and small molecules such as 2,2'-(methylimino) di (8-quinolinol) that inhibited metastatic growth of cancer cells. In addition, β1-integrin inhibitors have been or are being evaluated in clinical trials including ATN-161, a peptide derived from the sequence of fibronectin that act as an antagonist, volociximab, a humanized monoclonal antibody, and JSM6427, is a highly selective small-molecule. Overall, current studies indicated the importance of targeting β1-integrin as a new paradigm for metastasis prevention, and revealed its therapeutic advantage in treatment of patients with aggressive cancers.
  • Keywords: β1-integrin, Targeted therapy, Mestastasis.