TY - JOUR
TI - Clusterin overexpression in mice exacerbates diabetic phenotypes but suppresses tumor progression in a mouse melanoma model.
AU - Cheimonidi, Christina
AU - Grivas, Ioannis N.
AU - Sesti, Fabiola
AU - Kavrochorianou, Nadia
AU - Gianniou, Despoina D.
AU - Taoufik, Era
AU - Badounas, Fotis
AU - Papassideri, Issidora
AU - Rizzi, Federica
AU - Tsitsilonis, Ourania E.
AU - Haralambous, Sylva
AU - Trougakos, Ioannis P.
JO - Nature aging
PY - 2021
VL - 13
TODO - 5
SP - 6485--6505
PB - 
SN - null
TODO - 10.18632/aging.202788
TODO - Animals, Disease Models, Animal, *cancer, Disease Progression, Liver/metabolism, Pancreas/metabolism, Blood Glucose, Mice, Transgenic, *diabetes, *proteostasis, Clusterin/genetics/*metabolism, *chaperone, *clusterin, Melanoma/metabolism/*pathology
TODO - Clusterin (CLU) is an ATP-independent small heat shock protein-like chaperone, which functions both intra- and extra-cellularly. Consequently, it has been functionally  involved in several physiological (including aging), as well as in pathological  conditions and most age-related diseases, e.g., cancer, neurodegeneration, and  metabolic syndrome. To address CLU function at an in vivo model we established CLU  transgenic (Tg) mice bearing ubiquitous or pancreas-targeted CLU overexpression  (OE). Our downstream analyses in established Tg lines showed that ubiquitous or  pancreas-targeted CLU OE in mice affected antioxidant, proteostatic and metabolic  pathways. Targeted OE of CLU in the pancreas, which also resulted in CLU  upregulation in the liver likely via systemic effects, increased basal glucose  levels in the circulation and exacerbated diabetic phenotypes. Furthermore, by  establishing a syngeneic melanoma mouse tumor model we found that ubiquitous CLU OE  suppressed melanoma cells growth, indicating a likely tumor suppressor function in  early phases of tumorigenesis. Our observations provide in vivo evidence  corroborating the notion that CLU is a potential modulator of metabolic and/or  proteostatic pathways playing an important role in diabetes and tumorigenesis.
ER -