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The role of p130Cas substrate domain mediated signaling in cancer cell migration, invasiveness and metastasis of cancer cells
Zemanová, Kateřina ; Brábek, Jan (advisor) ; Čáslavský, Josef (referee)
p130Cas (Crk-associated substrate) was first described over 30 years ago as a protein that associates with the v-src and v-crk oncoproteins and undergoes tyrosine phosphorylation. Proteins of the CAS family are an important part of cellular biological processes in normal and pathological situations. The existence of 15 YXXP repetitive motifs is characteristics for substrate domain. p130Cas is an adapter protein that allows interactions between proteins that lead to assembly of multiprotein complexes. The p130Cas protein regulates these multiprotein complexes, which further drive chemotaxis, apoptosis, differentiation and migration. Overproduction of CAS proteins was found in connection with a poor prognosis and an increased incidence of metastases. Also, the elevated expression of proteins of the CAS family is related to resistance to some types of chemotherapeutics.
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The role of p130Cas substrate domain mediated signaling in cancer cell migration, invasiveness and metastasis of cancer cells
Zemanová, Kateřina ; Brábek, Jan (advisor) ; Čáslavský, Josef (referee)
p130Cas (Crk-associated substrate) was first described over 30 years ago as a protein that associates with the v-src and v-crk oncoproteins and undergoes tyrosine phosphorylation. Proteins of the CAS family are an important part of cellular biological processes in normal and pathological situations. The existence of 15 YXXP repetitive motifs is characteristics for substrate domain. p130Cas is an adapter protein that allows interactions between proteins that lead to assembly of multiprotein complexes. The p130Cas protein regulates these multiprotein complexes, which further drive chemotaxis, apoptosis, differentiation and migration. Overproduction of CAS proteins was found in connection with a poor prognosis and an increased incidence of metastases. Also, the elevated expression of proteins of the CAS family is related to resistance to some types of chemotherapeutics.
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The effect of Crk SH3domain inhibition in invasiveness of cells
Tomášová, Lea ; Rösel, Daniel (advisor) ; Vomastek, Tomáš (referee)
Protooncogene Crk was found to be upregulated in tumours with aggressive and invasive potential. The adaptor protein Crk has an important role in cell signaling: it integrates signals from activated integrins and growth factors receptors via its SH2 domain and transmits the signal to its SH3 domain binding partners that activate the small GTPases Rac1, Rap1 and Ras. This leads to regulation of cell migration, proliferation and survival. The aim of this thesis project was to inhibit the Crk dependent signaling by a competitive inhibition of the Crk SH3 domain, using a high affinity CrkSH3 binding peptoid. Binding of the inhibitor to the Crk SH3 domain prevents binding of cellular Crk SH3 interaction partners and the corresponding signal transmission is impaired. In this thesis project the effect of the Crk SH3 inhibition on the invasiveness of cancer cells was analyzed. The observed inhibitory effect on cell invasion as well as on anchorage independent growth provides a proof of therapeutical relevance of targeting CrkSH3N domain by peptoide-based inhibitors. Powered by TCPDF (www.tcpdf.org)
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