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The protein kinase encoded by the Akt proto-oncogene is activated by phospholipid binding, membrane translocation and phosphorylation. To address the relative roles of these mechanisms of Akt activation, we have employed a combination of genetic and pharmacological approaches. Transient transfection of NIH3T3 cells with wild-type Akt, pleckstrin homology(More)
Pancreatic cancer is almost always fatal, in part because of its delayed diagnosis, poor prognosis, rapid progression and chemoresistance. Oncogenic proteins are stabilized by the Hsp90, making it a potential therapeutic target. We investigated the oxidative stress-mediated dysfunction of Hsp90 and the hindrance of its chaperonic activity by a carbazole(More)
One of the major prognostic factors in rectal cancer is lymph node metastasis. The formation of lymph node metastases is dependent on the existence of a premetastatic niche. An important factor preceding metastasis are lymph vessels which are located in the lymph node. Accordingly, the occurrence of intranodal lymphangiogenesis is thought to indicate(More)
The Akt protooncogene encodes a serine-threonine protein kinase which is activated by growth factor-generated signals that are transduced via the phosphatidylinositol 3'-kinase (PI3-K). Earlier studies suggested that the activation of Akt by PI3-K may be mediated by the binding of D3-phosphorylated phosphoinositides to the Akt pleckstrin homology (PH)(More)
The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in patients with VHL disease and in the majority of patients with sporadic renal cell carcinomas (RCCs). RCCs are dependent on insulin-like growth factor-I receptor-mediated signaling for tumor growth and invasion in vivo. Reintroduction of the VHL gene product (pVHL) can inhibit on insulin-like(More)
PURPOSE Macroautophagy is a catabolic pathway that degrades cellular components through the lysosomal machinery. Cytoplasmic components are sequestered in double-membrane autophagosomes. They fuse with lysosomes where their cargo is delivered for degradation and recycling. Autophagy acts as a survival mechanism under stress by producing energy and as an(More)
Recurrence and subsequent metastatic transformation of cancer develops from a subset of malignant cells, which show the ability to resist stress and to adopt to a changing microenvironment. These tumor cells have distinctly different growth factor pathways and antiapoptotic responses compared with the vast majority of cancer cells. Long-term therapeutic(More)
Understanding the molecular mechanisms promoting therapy resistance is important. Previously, we reported that VEGFC can promote cancer cell survival during stress via interaction with its receptor NRP2. While examining the molecular mechanisms involved in this survival, we performed a microarray study in which we identified two genes, WDFY1 and LAMP2,(More)
A major contributor to cancer mortality is recurrence and subsequent metastatic transformation following therapeutic intervention. Therefore, in order to develop new treatment modalities and improve the efficacy of current ones, it is important to understand the molecular mechanisms that promote resistance to therapy in cancer cells. One pathway(More)
BACKGROUND Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF-A) is expressed constitutively in the adult glomerular podocytes at high levels; however, the regulation of its production is unclear. Recent data from podocyte-specific knockout mice suggest that VPF/VEGF-A is critical for the proper maintenance of glomerular filtration(More)