By Barbara A. Yoshida, Zita Dubauskas (auth.), Danny R. Welch (eds.)

Being clinically determined with melanoma is devastating. but if the melanoma cells need to unfold to shape secondary colonies, the diagnosis for the sufferer is worse. If significant advancements in survival are to ensue, then regulate of metastasis could be a origin. quite little is understood concerning the keep watch over of the metastatic method on the molecular point. This quantity starts off to discover our present wisdom in regards to the underlying molecular and biochemical mechanisms controlling the metastatic phenotype. whereas the entire authors tried to place their findings right into a context for translation to the scientific state of affairs, the state of the art doesn't totally let this. still, we write those summaries of our paintings as an early attempt towards that finish. i'm thankful to all the authors who've contributed generously in their time and energies to make this quantity a truth. To metastasize, neoplastic cells dissociate from the first tumor, input a circulatory compartment (typically lymphatics or blood vasculature), continue to exist shipping, arrest, go out the move and at last proliferate at a discontinuous web site in keeping with neighborhood progress elements. except cells accomplish each step of the metastatic cascade, metastases can't strengthen. the method is very inefficient, i. e. ,

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Location of KAI1 on the short arm of human chromosome 11 and frequency of allelic loss in advanced human prostate cancer. Prostate 1997; 32:205-13. 101. Dong JT, Lamb PW, Rinker-Schaeffer CW, et al. 2 [see comments]. Science 1995; 268:884-6. 102. Gao AC, Lou W, Dong JT, Isaacs JT. CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. Cancer Res 1997; 57:846-9. 103. Ueda T, Ichikawa T, Tamaru J, et al. Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.

39. Chambers AF, MacDonald IC, Schmidt EE, Morris VL, Groom AC. Clinical targets for anti-metastasis therapy [In Process Citation]. Adv Cancer Res 2000; 79:91-121. 40. Yang M, Jiang P, Sun FX, et al. A fluorescent orthotopic bone metastasis model of human prostate cancer. Cancer Res 1999; 59:781-6. 41. Chambers AF, MacDonald IC, Schmidt EE, et al. Steps in tumor metastasis: new concepts from intravital videomicroscopy. Cancer Metastasis Rev 1995; 14:279-301. 42. MacDonald IC, Schmidt EE, Morris VL, Groom AC, Chambers AF.

MEKK1 is not the only activator of SEK1/MKK4 and the SAPK cascade. Multiple protein kinases from different families are capable of activating SEK1/MKK4 and thus function as MEKKs (11, 14). This diversity of upstream activators likely reflects the incredible diversity of stimuli that converge at activation of the SAPKs. MEKKs in the p38 cascade have not been clearly identified. g. osmolar stress vs inflammatory cytokines). However, for many stimuli, one family of kinases highly conserved throughout evolution is likely to play a critical role.

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