Clusterin overexpression in mice exacerbates diabetic phenotypes but suppresses tumor progression in a mouse melanoma model.

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3215617 38 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Clusterin overexpression in mice exacerbates diabetic phenotypes but suppresses tumor progression in a mouse melanoma model.
Περίληψη:
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.
Έτος δημοσίευσης:
2021
Συγγραφείς:
Cheimonidi, Christina
Grivas, Ioannis N.
Sesti, Fabiola
Kavrochorianou, Nadia
Gianniou, Despoina D.
Taoufik, Era
Badounas, Fotis
Papassideri, Issidora
Rizzi, Federica
Tsitsilonis, Ourania E.
Haralambous, Sylva
Trougakos, Ioannis P.
Περιοδικό:
Nature aging
Τόμος:
13
Αριθμός / τεύχος:
5
Σελίδες:
6485--6505
Λέξεις-κλειδιά:
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
Επίσημο URL (Εκδότης):
DOI:
10.18632/aging.202788
Το ψηφιακό υλικό του τεκμηρίου δεν είναι διαθέσιμο.