Conza, Domenico (2017) The role of Endoplasmic Reticulum stress and GRP78 in endometrial cancer. [Tesi di dottorato]

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Tipologia del documento:	Tesi di dottorato
Lingua:	English
Titolo:	The role of Endoplasmic Reticulum stress and GRP78 in endometrial cancer
Autori:	Autore Email Conza, Domenico domenico.conza@libero.it
Data:	10 Aprile 2017
Numero di pagine:	64
Istituzione:	Università degli Studi di Napoli Federico II
Dipartimento:	Scienze Mediche Traslazionali
Dottorato:	Medicina clinica e sperimentale
Ciclo di dottorato:	29
Coordinatore del Corso di dottorato:	nome email Marone, Gianni frapagra@hotmail.com
Tutor:	nome email Formisano, Pietro [non definito]
Data:	10 Aprile 2017
Numero di pagine:	64
Parole chiave:	ER stress, GRP78, Endometrial cancer
Settori scientifico-disciplinari del MIUR:	Area 06 - Scienze mediche > MED/05 - Patologia clinica
Depositato il:	02 Mag 2017 08:22
Ultima modifica:	13 Mar 2018 10:30
URI:	http://www.fedoa.unina.it/id/eprint/11743
DOI:	10.6093/UNINA/FEDOA/11743

Abstract

Endometrial cancer is the most common malignancy of the female genital tract. However, in spite of a huge advance in our understanding of endometrial cancer biology, therapeutic modalities haven't significantly changed over the past 40 years. Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development and progression. Our previous studies reported for the first time that GRP78 is increased in endometrial tumors. In this study, we further analyzed the role of UPR and GRP78 in endometrial cancer progression. We found that GRP78 plays a role in endometrial cancer progression since its silencing attenuate both the growth and invasion of endometrial cancer cells. Interestingly, we also show that metformin, an antidiabetic drug with anticancer properties, is able to inhibit endometrial cancer cells growth and this is accompanied by the inhibition of GRP78 expression and upregulation of proapoptotic UPR genes such as ATF4 and CHOP. Finally, we describe that metformin affects β-catenin signaling, a frequently activated signaling pathway in endometrial cancer. These observations highlight the possibility that GRP78 might represent an intriguing therapeutic target of metformin action in the treatment of endometrial cancer.

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