ampanella C

Mitochondrial Chaperones in Cancer From Molecular Biology to Clinical Diagnostics

Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also been previously studied as markers of tumorigenesis. Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation, DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization. This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HSP10 complex and their modifications leading to cell transformation and cancer development. These molecules could represent modern molecular biomarkers for oncological management.

Heat shock protein 10 and signal transduction: a ''capsula eburnea'' of carcinogenesis?

Abstract To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data suggest that Hsp10 may be not only a component of the folding machine but also an active player of the cell signaling network, influencing cell cycle, nucleocytoplasmic transport, and metabolism, with putative roles in the lack of cell differentiation and in the inhibition of apoptosis. In this review, we revise the involvement of Hsp10 in signal transduction pathways and its possible role in cancer etiology.

The value of immunohistochemical research on PCNA, p53 and heat shock proteins in prostate cancer management: a review

This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagnosis, mainly because of the controversy regarding the significance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We briefly describe the physiological roles of Hsps in normal cells, and the significance of their immunohistochemical detection in PC as well as in pre-cancerous lesions of the prostate. We will also discuss the possible functional interactions of these molecules in both dysplastic and neoplastic cells.

Human Recombinant Vasostatin‐1 May Interfere with Cell–Extracellular Matrix Interactions

Abstract:u2002 Vasostatin‐1 (VS‐1), the N‐terminal fragment derived from the cleavage of chromogranin A (CgA), has been shown to exert several biological activities on several tissues and organs. Recently, it has been reported that human recombinant VS‐1 (STA‐CGA1‐78) may alter myocardial contractility in eel, frog, and rat hearts. In this article we have explored if STA‐CGA1‐78 can induce intracellular cascades interacting both with adhesion molecules and/or extracellular matrix (ECM), components, that is, involvement of the heat shock protein 90 (HSP90) and the endothelial NOS (eNOS), known to be implicated in signal transduction mechanisms affecting myocardial contractility. We used 3D cultured adult rat cardiomyocytes cultivated over fibronectin or fibroblasts or embedded in matrigel or collagen type I. Aurion‐conjugated VS‐1 (Au‐STA‐CGA1‐78) has been used to identify possible sites of interaction of this molecule with the cell membrane. We found that in our 3D culture, cell–ECM interactions played a crucial role in the cellular localization of HSP90 as well as in the expression of eNOS. VS‐1 appeared to modulate cell–ECM interactions, thereby remarkably leading to a different cellular localization of HSP90. Moreover, Au‐STA‐CGA1‐78 was never detected inside the cell nor overlapping the plasma membrane, but nearby the outer side of the cardiomyocyte plasmalemma, at a particular distance, typical of integrins. On the whole, these data suggest that VS‐1 does not have a classic receptor on the membrane but that integrins may represent a nonconventional VS‐1 receptor modulating eNOS signaling pathway.