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In this study, a novel and unexpected role of the armadillo repeat protein p0071 in cellular transport is described. P0071 abrogation in cultured cells significantly interferes with secretion of various secretory cargo proteins. This effect is specifically targeting cargo substrates of the microtubule based heterotrimeric kinesin-2 complex, which comprises of KIF3A, KIF3B and KAP3. Impairment of both p0071 and KIF3B leads to aberrant movement of chromogranin A granules in neuroendocrine tumor cells due to impaired directional persistence of vesicle transport. This effect is likely explained by a potential function of p0071 as a stabilizing linker within the kinesin-2 complex since it could be shown that p0071 mediates the interaction between the motor subunit KIF3B and the cargo-adaptor subunit, KAP3.

IHC of pancreatic cancer cells growing on CAM using specific antibodies directed against desmin and von Willebrand factor (vWF) is presented. The images reveal both intratumoral and extratumoral immunoreactivity of the endothelial markers. (PPTX 4480 kb)

PKM2 abrogation results in decreased blood vessel formation in vivo. IHC of BxPC3 pancreatic cancer cells growing on CAM using specific antibodies for desmin and von Willebrand factor (vWF) is presented. (PPTX 3897 kb)

PKM2 regulates hypoxia-induced HIF-1α accumulation. A, B, pancreatic cancer cells transduced with a non-targeting control shRNA or PKM2-specific shRNAs were incubated under hypoxia or normoxia for 8 h. HIF-1α levels were determined using western blot analysis. Quantification of HIF-1α band intensity was conducted using ImageJ software (No – normoxia; Hy – hypoxia). (PPTX 72 kb)

PKM2 regulates hypoxia-induced VEGF promoter activity. A, PaTu2 cancer cells were transiently transfected with 3xHRE-luc and pTK-Renilla. Four hours after transfection cells were incubated under normoxic or hypoxic conditions in the absence or presence of 30 μM TEPP-46. Cell lysates were subjected to luciferase assay. Bars are the means +/- SEM of at least two independent experiments performed in duplicate. B, cancer cells were transiently transfected with VEGF-luc and pTK-Renilla. Four hours after transfection cells were incubated under normoxic or hypoxic conditions in the absence or presence of 30 μM TEPP-46. Cell lysates were subjected to luciferase assay. Bars are the means +/- SEM of at least two independent experiments performed in duplicate. C, D, PaTu2 and Capan1 cells were transiently transfected with VEGF-luc reporter. Four hours later cells were incubated under normoxic or hypoxic conditions in the absence or presence of 10 μM BAY 87-2243. Lysates were subjected to luciferase assay. Bars are the means +/- SEM of at least two independent experiments performed in duplicate (No – normoxia; Hy – hypoxia). (PPTX 138 kb)

34 human pancreatic specimens were stained with PKM2 and CD31 antibodies. Representative images are shown. (PPTX 760 kb)

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 2009