New insights into the metastasis-associated 67 kD laminin receptor.
The interactions between tumor cells and laminin or other components of the extracellular matrix have been shown to play an important role in tumor invasion and metastasis. These interactions are mediated by different cell surface molecules, including the monomeric 67 kD laminin receptor. This molecule appears to be very peculiar since so, far only a full-length gene encoding a 37 kD precursor protein has been isolated and the mechanism by which the precursor reaches the mature form is not understood. Based on clinical data, which clearly demonstrate the importance of the receptor in tumor progression, studies were conducted to define the structure, expression, and function of this laminin receptor as a step toward developing therapeutic strategies that target this molecule. The data suggest that acylation of the precursor is the key mechanism in maturation of the 67 kD form. The function of the membrane receptor is to stabilize the binding of laminin to cell surface integrins, acting as an integrin-accessory molecule, although homology of the gene encoding the receptor precursor with other genes suggests additional functions. Downregulation of the receptor expression on tumor cells might open new therapeutic approaches to decrease tumor aggressiveness.
Ménard
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Division of Experimental Oncology E, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. menard@istitutotumori.mi.it
Castronovo
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V
Tagliabue
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Sobel
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ME
D000818:Animals; D018076:DNA, Complementary / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D007797:Laminin / Q000502:physiology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics; D017474:Receptors, Laminin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D017385:Sequence Homology
D018076:DNA, Complementary; D007797:Laminin; D017474:Receptors, Laminin