Your browser doesn't support javascript.
loading
Protease-activated receptors (PARs) in cancer: Novel biased signaling and targets for therapy.
Bar-Shavit, R; Maoz, M; Kancharla, A; Jaber, M; Agranovich, D; Grisaru-Granovsky, S; Uziely, B.
Afiliación
  • Bar-Shavit R; Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Maoz M; Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Kancharla A; Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Jaber M; Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Agranovich D; Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Grisaru-Granovsky S; Department of Obstetrics and Gynecology, Shaare Zedek, Jerusalem, Israel.
  • Uziely B; Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Methods Cell Biol ; 132: 341-58, 2016.
Article en En | MEDLINE | ID: mdl-26928551
Despite the fact that G protein-coupled receptors (GPCRs) mediate numerous physiological processes and represent targets for therapeutics for a vast array of diseases, their role in tumor biology is under appreciated. Protease-activated receptors (PARs) form a family which belongs to GPCR class A. PAR1&2 emerge with a central role in epithelial malignancies. Although the part of PAR1&2 in cancer is on the rise, their underlying signaling events are poorly understood. We review hereby past, present, and future cancer-associated PAR biology. Mainly, their role in physiological (placenta-cytotophobalst) and patho-physiological invasion processes. The identification and characterization of signal pleckstrin homology (PH)-domain-binding motifs established critical sites for breast cancer growth in PAR1&2. Among the proteins found to harbor important PH-domains and are involved in PAR biology are Akt/PKB as also Etk/Bmx and Vav3. A point mutation in PAR2, H349A, but not R352A, abrogated PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumor growth in vivo as also placental extravillous trophoblast (EVT) invasion in vitro is markedly reduced. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind PH-domain, inhibits mammary tumors and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Transducción de Señal / Receptores Proteinasa-Activados / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Methods Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Transducción de Señal / Receptores Proteinasa-Activados / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Methods Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos