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Vimentin is a novel AKT1 target mediating motility and invasion.

Oncogene | Jan 27, 2011

The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a potential cell type and isoform type-specific AKT-driven function. By implication, study of AKT signaling should optimally be conducted in an appropriate intracellular environment. Prognosis in soft-tissue sarcoma (STS), the aggressive malignancies of mesenchymal origin, is poor, reflecting our modest ability to control metastasis, an effort hampered by lack of insight into molecular mechanisms driving STS progression and dissemination. We examined the impact of the cancer progression-relevant AKT pathway on the mesenchymal tumor cell internal milieu. We demonstrate that AKT1 activation induces STS cell motility and invasiveness at least partially through a novel interaction with the intermediate filament vimentin (Vim). The binding of AKT (tail region) to Vim (head region) results in Vim Ser39 phosphorylation enhancing the ability of Vim to induce motility and invasion while protecting Vim from caspase-induced proteolysis. Moreover, vimentin phosphorylation was shown to enhance tumor and metastasis growth in vivo. Insights into this mesenchymal-related molecular mechanism may facilitate the development of critically lacking therapeutic options for these devastating malignancies.

Pubmed ID: 20856200 RIS Download

Mesh terms: Animals | Blotting, Western | Cell Line, Tumor | Cell Movement | Fluorescent Antibody Technique | Humans | Immunoprecipitation | Mesoderm | Mice | Mice, SCID | Neoplasm Invasiveness | Proto-Oncogene Proteins c-akt | Sarcoma | Signal Transduction | Soft Tissue Neoplasms | Transfection | Vimentin

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Associated grants

  • Agency: NHLBI NIH HHS, Id: N01HV28184
  • Agency: NCI NIH HHS, Id: R01 CA138345
  • Agency: NHLBI NIH HHS, Id: N01-HV-28184
  • Agency: NCI NIH HHS, Id: CA138345
  • Agency: NCI NIH HHS, Id: R01 CA138345-02

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Scansite searches for motifs within proteins that are likely to be phosphorylated by specific protein kinases or bind to domains such as SH2 domains, 14-3-3 domains or PDZ domains. The Motifscanner program utilizes an entropy approach that assesses the probability of a site matching the motif using the selectivity values and sums the logs of the probability values for each amino acid in the candidate sequence. The program then indicates the percentile ranking of the candidate motif in respect to all potential motifs in proteins of a protein database. When available, percentile scores of some confirmed phosphorylation sites for the kinase of interests or confirmed binding sites of the domain of interest are provided for comparison with the scores of the candidate motifs.


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Fisher Center For Alzheimers Research Foundation: ALZinfo.org

A portal to educate, engage and create an online community. The Fisher Center for Alzheimer''s Research Foundation, founded in 1995, was created in answer to the recommendations of three U.S. Senate commissioned symposia held in the 1990s by the National Institutes of Health (NIH) to gather information on the cause, care and cure of Alzheimer''s disease. The Fisher Center was created following this design. The funding initiatives of the Foundation are appropriated accordingly to the three areas cited by the NIH task force cause, care and cure. The primary resources of the Foundation are directed toward scientific research into the cause and hopefully the cure of Alzheimer''s disease. To this end, the Foundation under the direction of its founder, Zachary Fisher, and in collaboration with David Rockefeller, constructed the Fisher Center for Alzheimer''s Disease Research at The Rockefeller University, headed by 2000 Nobel Prize winner, Paul Greengard, Ph.D. The 10,000 square foot laboratory is the most advanced facility of its kind in the country equipped with the latest in equipment necessary to undertake an interdisciplinary assault on this disease. The Fisher Center also has collaborative programs at the University of Genoa and supports the work of well over 60 scientists and researchers across the United States and in 17 foreign countries. The Foundation also funds projects for the care of people with Alzheimer''s disease and their caregivers. The Fisher Alzheimer''s Disease Education and Resources Program at the New York University School of Medicine was established under the direction of Barry Reisberg, M.D., internationally known expert in the care of Alzheimer''s patients. The Foundations Alzheimer''s Information Program was created in 2001 to answer the primary need of caregivers for comprehensive, easily accessible information. Our goals are to: Understand the Cause of Alzheimer''s To find a Cure for this devastating disease Improve the Care of people living with the disease to enhance their quality of life and that of their caregivers and families About Our Research Beating Back Beta Amyloid Improving the Quality of Life for Alzheimers Patients Reversing Nerve Cell Damage Using Hormones to Slow the Progress of Disease Curing Early-Onset Alzheimers The Science of Caregiving Scientific Studies


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