By a News Reporter-Staff News Editor at Biotech Week -- Researchers detail new data in Enzymes and Coenzymes. According to news originating from Paris, France, by NewsRx correspondents, research stated, "The immunogenic demise of cancer cells can be induced by various chemotherapeutics, such as anthracyclines and oxaliplatin, and provokes an immune response against tumor-associated antigens. Thus, immunogenic cell death (ICD)-inducing antineoplastic agents stimulate a tumor-specific immune response that determines the long-term success of therapy."
Our news journalists obtained a quote from the research from Georges Pompidou European Hospital, "The release of ATP from dying cells constitutes one of the three major hallmarks of ICD and occurs independently of the two others, namely, the pre-apoptotic exposure of calreticulin on the cell surface and the postmortem release of high-mobility group box 1 (HMBG1) into the extracellular space. Pre-mortem autophagy is known to be required for the ICD-associated secretion of ATP, implying that autophagy-deficient cancer cells fail to elicit therapy-relevant immune responses in vivo. However, the precise molecular mechanisms whereby ATP is actively secreted in the course of ICD remain elusive. Using a combination of pharmacological screens, silencing experiments and techniques to monitor the subcellular localization of ATP, we show here that, in response to ICD inducers, ATP redistributes from lysosomes to autolysosomes and is secreted by a mechanism that requires the lysosomal protein LAMP1, which translocates to the plasma membrane in a strictly caspase-dependent manner. The secretion of ATP additionally involves the caspase-dependent activation of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1)-mediated, myosin II-dependent cellular blebbing, as well as the opening of pannexin 1 (PANX1) channels, which is also triggered by caspases. Of note, although autophagy and LAMP1 fail to influence PANX1 channel opening, PANX1 is required for the ICD-associated translocation of LAMP1 to the plasma membrane."
According to the news editors, the research concluded: "Altogether, these findings suggest that caspase-and PANX1-dependent lysosomal exocytosis has an essential role in ATP release as triggered by immunogenic chemotherapy."
For more information on this research see: Molecular mechanisms of ATP secretion during immunogenic cell death. Cell Death and Differentiation, 2014;21(1):79-91. Cell Death and Differentiation can be contacted at: Nature Publishing Group, Macmillan Building, 4 Crinan St, London N1 9XW, England. (Nature Publishing Group - www.nature.com/; Cell Death and Differentiation - www.nature.com/cdd/)
The news correspondents report that additional information may be obtained from I. Martins, Hopital Europeen Georges Pompidou, AP HP, Pole Biol, F-75015 Paris, France. Additional authors for this research include Y. Wang, M. Michaud, Y. Ma, A.Q. Sukkurwala, S. Shen, O. Kepp, D. Metivier, L. Galluzzi, J.L. Perfettini, L. Zitvogel and G. Kroemer (see also Enzymes and Coenzymes).
Keywords for this news article include: Paris, Drugs, France, Europe, Caspases, Chemotherapy, Peptide Hydrolases, Enzymes and Coenzymes, Cysteine Endopeptidases
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC