AIRC LUINI 2018Dissecting and targeting the oncogenic molecular mechanism of action of Golph3, a regulator of Golgi traffic. (DSB.AD001.108)

Area tematica

Scienze biomediche

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto degli Endotipi in Oncologia, Metabolismo e Immunologia "G. Salvatore" (IEOMI)

Altre strutture che collaborano al progetto di ricerca

• Istituto di Biochimica e Biologia Cellulare (IBBC)

Responsabile di progetto

ALBERTO LUINI
Telefono: 0816132722
E-mail: a.luini@ibp.cnr.it

Abstract

A focal amplification in the chromosomal region 5p13 has been identified as a frequent copy-number-variation in cancer
samples. Among genes located on 5p13, GOLPH3 was found to cause tumoral transformation as it stimulates uncontrolled cell
proliferation when overexpressed. GOLPH3 encodes a cytosolic protein that is dynamically recruited to the trans face of the
Golgi complex and that is involved in membrane trafficking events. The molecular bases of GOLPH3 mediated oncogenesis are
to date not defined.
The main hypothesis is that GOLPH3, an abundant Golgi protein and a powerful oncogene in many solid tumors, acts by
accelerating the intra-Golgi recycling of a set of Golgi glycosylating enzymes. These enzymes gain function as a result of
changes of their levels and of their Golgi localization. Many of these enzymes, including lactosyl-ceramide synthase (LCS),
regulate the metabolism of glycosphingolipids, which are involved in cancer. Therefore GOLPH3 might exert its oncogene
activity through the changes in sphingolipid glycosylation and in ceramide levels.

Obiettivi

Our main aims are: a) to reach a satisfactory understanding of the multiple oncogenic mechanisms of GOLPH3, b) to delineate
the regulatory mechanisms impinging on GOLPH3, especially those that are involved in cancer and, c) to identify small
molecule inhibitors of the GOLPH3 oncogenic cascade with drug-like property for in vivo use as anticancer agents against
GOLPH3-dependent tumors.

Data inizio attività

02/01/2018

Parole chiave

Golgi, Lipid metabolism, Oncogenes

Ultimo aggiornamento: 15/06/2025