AIRC LUINI 2018Dissecting and targeting the oncogenic molecular mechanism of action of Golph3, a regulator of Golgi traffic. (DSB.AD001.108)
Thematic area
Project area
Oncologia e Immunologia (DSB.AD001)Structure responsible for the research project
Institute Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOS)
Other structures collaborating in the research project
Project manager
ALBERTO LUINI
Phone number: 0816132722
Email: 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.
Goals
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.
Start date of activity
02/01/2018
Keywords
Golgi, Lipid metabolism, Oncogenes
Last update: 25/04/2024