Fibronectin and its alpha 5 beta 1 integrin receptor in malignancy.
Fibronectin and the alpha 5 beta 1 integrin play complex roles in malignancy. While normal cells usually deposit a fibronectin matrix around themselves, malignant cell lines often fail to do so. Decreased expression of the alpha 5 beta 1 integrin, which directs fibronectin matrix deposition, is one of the reasons for deficient matrix deposition. The defect can be corrected by expression of additional alpha 5 beta 1 from transfected cDNAs and exacerbated by selecting cells for loss of all alpha 5 beta 1. Tumorigenicity is suppressed in the alpha 5 beta 1 overexpressors and enhanced in the alpha 5 beta 1-negative cells. Synthetic peptides that bind to the alpha 5 beta 1 and other integrins can modulate their functions and suppress malignancy and metastasis in vivo. The signaling mechanisms that underlie these tumor-suppressive effects of the fibronectin matrix and the integrins are an important target for ongoing study.
Ruoslahti
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Cancer Research Center, La Jolla Cancer Research Foundation, Calif 92037, USA.
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D017469:Receptors, Fibronectin / Q000502:physiology*
D005353:Fibronectins; D016023:Integrins; D017469:Receptors, Fibronectin