Liver is an important secretory organ that consistently manages various insults in order to retain whole-body homeostasis. Importantly, it was suggested that the tumor-suppressor p53 plays a role in a variety of liver physiological processes and thus it is being regarded as a systemic homeostasis regulator. Using high-throughput mass spectrometric analysis, we identified various p53-dependent liver secretome profiles. This allowed a global view on the role of p53 in maintaining the harmony of liver and whole-body homeostasis. We found that p53 altered the liver secretome differently under various conditions. Under physiological conditions, p53 controls factors that are related mainly to lipid metabolism and injury response. Upon exposure to various types of cancer therapy agents, the hepatic p53 is activated and induces the secretion of proteins related to additional pathways, such as hemostasis, immune response, and cell adhesion. Interestingly, we identified a possible relationship between p53-dependent liver functions and lung tumors. The latter modify differently liver secretome profile toward the secretion of proteins mainly related to cell migration and immune response. The notion that p53 may rewire the liver secretome profile suggests a new non-cell autonomous role of p53 that affect different liver functions and whole organism homeostasis.
Bibliographical noteFunding Information:
We wish to thank Dr. Ori Brenner for tumor histology analysis, to Dr. Raya Eilam for the help with Immunohistochemistry staining, to Dr. Meital Kupervaser at the de Botton Institute for Protein Profiling, and The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science for the mass spectrometric analysis. This research was supported by the Center of Excellence from Flight Attendant Medical Research Institute (FAMRI) and from the Israel Science Foundation (ISF). This publication reflects the authors’ views and not necessarily those of the European Community. V.R. is the incumbent of the Norman and Helen Asher Professorial Chair Cancer Research at the Weizmann institute.
© 2018 The Author(s).