Pathways of metastasis suppression in bladder cancer.
Despite the recent advances in the diagnosis of bladder cancer, recurrence after surgical intervention for muscle invasive disease is still problematic as nearly half of the patients harbor occult distant metastases and this, in turn, is associated with poor 5-year survival rate. We have recently identified Rho family GDP dissociation inhibitor 2 (RhoGDI2) protein as functional metastasis suppressor and a prognostic marker in patients after cystectomy. In identifying the mechanisms underlying metastasis suppression by RhoGDI2, we found this protein to be associated with the c-Src kinase in human tumors, where the expression of both is diminished as a function of stage. Interestingly, c-Src bound to and phosphorylated RhoGDI2 resulting in enhanced metastasis suppressive potency. In this review, we will discuss the established roles of c-Src and RhoGDI2 in bladder cancer and speculate on their therapeutic relevance.
Said
Neveen
N
Department of Urology, University of Virginia, Box 800422, Charlottesville, VA 22908, USA.
Theodorescu
Dan
D
D000595:Amino Acid Sequence; D000081247:CSK Tyrosine-Protein Kinase; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D017124:Conserved Sequence; D015653:Cystectomy; D066246:ErbB Receptors / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D019061:src-Family Kinases / Q000502:physiology
C569658:ARHGDIB protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human