000			02680na a2200229 4500
003			PC4214
005			20210625062801.0
008			130622s2011 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_aMedraño Fernández, Iria _91623 _eInstituto de Investigación i+12
245	0	0	_aRap1-GTP-interacting Adaptor Molecule (RIAM) protein controls invasion and growth of melanoma cells _h[artículo]
260			_bJournal of Biological Chemistry, _c2011
300			_a286(21):18492-18504.
500			_aFormato Vancouver: Hernández-Varas P, Coló GP, Bartolomé RA, Paterson A, Medraño-Fernández I, Arellano-Sánchez N, et al. Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells. J Biol Chem. 2011;286(21):18492-504.
501			_aPMID: 21454517
504			_aContiene 38 referencias.
520			_aThe Mig-10/RIAM/lamellipodin (MRL) family member Rap1-GTP-interacting adaptor molecule (RIAM) interacts with active Rap1, a small GTPase that is frequently activated in tumors such as melanoma and prostate cancer. We show here that RIAM is expressed in metastatic human melanoma cells and that both RIAM and Rap1 are required for BLM melanoma cell invasion. RIAM silencing in melanoma cells led to inhibition of tumor growth and to delayed metastasis in a severe combined immunodeficiency xenograft model. Defective invasion of RIAM-silenced melanoma cells arose from impairment in persistent cell migration directionality, which was associated with deficient activation of a Vav2-RhoA-ROCK-myosin light chain pathway. Expression of constitutively active Vav2 and RhoA in cells depleted for RIAM partially rescued their invasion, indicating that Vav2 and RhoA mediate RIAM function. These results suggest that inhibition of cell invasion in RIAM-silenced melanoma cells is likely based on altered cell contractility and cell polarization. Furthermore, we show that RIAM depletion reduces beta 1 integrin-dependent melanoma cell adhesion, which correlates with decreased activation of both Erk1/2 MAPK and phosphatidylinositol 3-kinase, two central molecules controlling cell growth and cell survival. In addition to causing inhibition of cell proliferation, RIAM silencing led to higher susceptibility to cell apoptosis. Together, these data suggest that defective activation of these kinases in RIAM-silenced cells could account for inhibition of melanoma cell growth and that RIAM might contribute to the dissemination of melanoma cells.
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/4/pc4214.pdf _ySolicitar documento
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999			_c4214 _d4214