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Example sentences for: cathepsins

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Modulation of this mitogenic pathway occurs in part via the M6P/IGF2R, which functions in the internalization and degradation of IGF-II [ 10 ] . M6P/IGF2R is also important in activation of TGF-β, a potent growth inhibitor for most cell types, and in binding, transport and activation of lysosomal enzymes, such as cathepsins [ 12 13 ] . It has been shown that M6P/IGF2R expression is significantly reduced in both rat and human hepatocellular carcinomas [ 14 ] . Loss of hetorozygosity (LOH) at the M6P/IGF2 receptor gene locus on 6q26-27 coupled with somatic point mutations in the remaining allele has recently been demonstrated in liver and breast cancers [ 15 16 17 18 19 20 21 22 23 ] . In addition, somatic mutations of the M6P/IGF2R gene were also found in prostate cancer, lung carcinoma, and genetically unstable cancers of the endometrium, brain, stomach and colorectum [ 24 25 26 27 28 29 ] . The findings of LOH and mutations of M6P/IGF2R in a wide variety of tumor types have led to the proposition that the M6P/IGF2R is a tumor suppressor gene.
Recent evidence suggests that lysosomal enzymes, such as cathepsins B and D contribute to TNF-induced apoptosis in vitro [ 35 36 37 38 ] and in vivo [ 39 ] . The M6P/IGF2 receptor has been shown to be involved in binding, transport and activation of lysosomal enzymes, including cathepsins [ 12 13 ] . Therefore, it is possible that down-regulation of the M6P/IGF2R results in improper trafficking and activation of cathepsins.