Addicted to secrete - novel concepts and targets in cancer therapy.
The unfolded protein response (UPR) mediates the adaptation of the secretory pathway (SP) to fluctuations in cellular protein demand or to environmental variations. Recently, drug screenings have confirmed the therapeutic potential of targeting the UPR in cancer models. However, the UPR may not be the only druggable target of the SP. Moreover, recent studies have revealed other contributions of the SP to cancer development. This article does not intend to describe the well-established implication of UPR signaling pathways in cancer cell life and cell decision, but rather aims at defining the concept of 'tumor cell secretory addiction', from molecular, cellular, and therapeutic perspectives. Furthermore, the implication of UPR modulations in this context will be discussed.
Inserm U1053, F-33000 Bordeaux, France; University Bordeaux-Segalen, F-33000 Bordeaux, France. Electronic address: nicolas.dejeans@gmail.com.
Nicolas
N
Dejeans
University of Lyon, 69000 Lyon, France; UMR CNRS 5286, INSERM 1052, Cancer Research Center of Lyon, 69000 Lyon, France.
Serge
S
Manié
Biomedical Neuroscience Institute, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile; Neurounion Biomedical Foundation, Santiago, Chile; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Claudio
C
Hetz
Laboratory Regulation of Membrane Traffic, Institute of Molecular and Cell Biology, Singapore, Singapore; Department of Biochemistry, National University of Singapore, Singapore, Singapore.
Frédéric
F
Bard
Cell Signaling Unit, p53 Signal Transduction Laboratories, Edinburgh Cancer Research Centre, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
Ted
T
Hupp
Department of Cellular and Molecular Medicine, University of Leuven (KU Leuven), Leuven, Belgium.
Patrizia
P
Agostinis
Apoptosis Research Centre, School of Natural Sciences, NUI Galway, Galway, Ireland.
Afshin
A
Samali
Inserm U1053, F-33000 Bordeaux, France; University Bordeaux-Segalen, F-33000 Bordeaux, France; University of Lyon, 69000 Lyon, France. Electronic address: eric.chevet@inserm.fr.
Eric
E
Chevet
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055571:Secretory Pathway / Q000187:drug effects*; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000187:drug effects
D000970:Antineoplastic Agents; D011506:Proteins
cancer therapy; secretory pathway; unfolded protein response