Open AccessClusterin overexpression in mice exacerbates diabetic phenotypes but suppresses tumor progression in a mouse melanoma model
Author(s) -
Christina Cheimonidi,
Ioannis Grivas,
Fabiola Sesti,
Nadia Kavrochorianou,
Despoina D. Gianniou,
Era Taoufik,
Fotis Badounas,
Issidora S. Papassideri,
Federica Rizzi,
Ourania E. Tsitsilonis,
Sylva Haralambous,
Ioannis P. Trougakos
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202788
Subject(s) - clusterin , phenotype , melanoma , cancer research , tumor progression , medicine , biology , apoptosis , cancer , gene , genetics
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.