Open AccessThe unfolded protein response in glioblastomas: targetable or trouble?
Author(s) -
Michael W. Graner
Publication year - 2015
Publication title -
future science oa
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 23
ISSN - 2056-5623
DOI - 10.4155/fso.15.45
Subject(s) - unfolded protein response , endoplasmic reticulum , cancer research , biology , phenotype , angiogenesis , chaperone (clinical) , protein folding , cellular stress response , microbiology and biotechnology , fight or flight response , neuroscience , medicine , pathology , gene , genetics
Glioblastomas are devastating central nervous system tumors with abysmal prognoses. These tumors are often difficult to resect surgically, are highly invasive and proliferative, and are resistant to virtually all therapeutic attempts, making them universally lethal diseases. One key enabling feature of their tumor biology is the engagement of the unfolded protein response (UPR), a stress response originating in the endoplasmic reticulum (ER) designed to handle the pathologies of aggregating malfolded proteins in that organelle. Glioblastomas and other tumors have co-opted this stress response to allow their continued uncontrolled growth by enhanced protein production (maintained by chaperone-assisted protein folding) and lipid biosynthesis driven downstream of the UPR. These features can account for the extensive extracellular remodeling/invasiveness/angiogenesis and proliferative capacity, and ultimately result in tumor phenotypes of chemo- and radio-resistance. The UPR in general, and its chaperoning capacity in particular, are thus putative high-value targets for treatment intervention. Such therapeutic strategies, and potential problems with them, will be discussed and analyzed.