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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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Functional analysis of the internally disordered structure of the substrate domain in p130Cas protein biology
Hejnarová, Marie ; Rösel, Daniel (advisor) ; Gemperle, Jakub (referee)
The p130Cas protein is an important mechanosensor in cell adhesive structures such as focal adhesions and podosomes. There, the protein is subjected to mechanical tension that underlie its participation in integrin signaling. At the level of p130Cas, the mechanical force is transduced into a chemical signal. Although p130Cas does not exhibit enzymatic activity, its high binding potential turns it into an important signaling junction that ensures signal distribution to different cellular pathways. As a result, p130Cas has a profound effect on fun- damental cellular processes such as cell proliferation, differentiation and motility. In addition to its irreplaceable role in embryonic development, its involvement in the origin of patholo- gies has also been reported. As a major substrate for Src kinase, p130Cas can participate in signaling leading to tumor transformation and further malignant development. Its upregulated expression is ofen observed in aggressive types of metastasizing tumors, such as breast, prostate, and melanoma cancer. Therefore, in recent years, the possible use of the p130Cas protein as a potential target for migrastatics under development has been discussed. Within this thesis, we focus on the functional analysis of the p130Cas substrate domain. This domain is respon- sible for...
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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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