Laboratorio Of Oncologia Molecolare

Rionero in Vulture, Italy

Laboratorio Of Oncologia Molecolare

Rionero in Vulture, Italy

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Matassa D.S.,University of Naples Federico II | Amoroso M.R.,University of Naples Federico II | Maddalena F.,Laboratorio Of Oncologia Molecolare | Landriscina M.,University of Foggia | Esposito F.,University of Naples Federico II
American Journal of Cancer Research | Year: 2012

Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a mitochondrial heat shock protein involved in the protection from DNA damages and apoptosis induced by oxidants and several other stress conditions. Despite the well-characterized role in the regulation of mitochondrial integrity, through the interaction with cyclophilin D, a mitochondrial permeability transition pore regulator, several recent studies contributed to draw a more complex "picture" of the TRAP1 pathway: most of these updated functions arise from the identification of novel specific TRAP1 "client" proteins and from the recent discovery of multiple subcellular localizations/functions for this chaperone. This review briefly highlights some general features of TRAP1, and among others its role in cytoprotection, summarizing many different functions, which contribute to its protective role upon several stress inducers. Of note, particular emphasis is given to the recent findings on the regulation of Endoplasmic Reticulum stress and protein quality control by TRAP1, as well as to its role in regulating calcium homeostasis throughout its client protein Sorcin. Starting from the above observations a preliminary "TRAP1 signature" is provided and a new intriguing and interesting field to explore is discussed. Several questions are still open given the complexity of such mechanisms. However, by translating these recent insights at the molecular and cellular levels into personalized individual anticancer treatments, designing novel strategies based on the simultaneous inhibition of multiple tumor-specific pathways, and contemplating subcellular-targeted approaches aimed at reverting drug resistance and improving antitumor activity the struggle to combat cancer become more successful and closer.


Di Sanzo M.,University of Catanzaro | Gaspari M.,University of Catanzaro | Misaggi R.,University of Catanzaro | Romeo F.,University of Catanzaro | And 10 more authors.
Journal of Proteome Research | Year: 2011

Ferritin, the major intracellular iron-storage protein, is made of 24 subunits of two types, H and L. Besides regulating intracellular iron homeostasis, it has been found that ferritin, in particular the H subunit (FHC), is involved in different biological events such as cell differentiation and pathologic states (i.e., neurodegeneration and cancer). This study is aimed at investigating the whole-cell proteome of FHC-expressing and sh-RNA-silenced human metastatic melanoma cells (MM07 m) in the attempt to identify and classify the highest number of proteins directly or indirectly controlled by the FHC. We identified about 200 differentially expressed proteins and classified them in clusters on the basis of their functions, as proteins involved in metabolic processes, cell adhesion, migration, and proliferation processes. Some of them have captured our attention because of their involvement in metabolic pathways related to tumor progression and metastasis. In vitro assays confirmed that the FHC-silenced MM07 m cells are characterized by a decreased growth activity, a reduced invasiveness, and a reduced cell adhesion capability. Moreover, nude mice (CD1 nu/nu), subcutaneously injected with FHC-silenced MM07 m cells, showed a remarkable 4-fold reduction of their tumor growth capacity compared to those who received the FHC-unsilenced MM07 m counterpart. In conclusion, these data indicate that gene silencing technology, coupled to proteomic analysis, is a powerful tool for a better understanding of H ferritin signaling pathways and lend support to the hypothesis that specific targeting of this gene might be an attractive and potentially effective strategy for the management of metastatic melanoma. © 2011 American Chemical Society.

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