MECHANISMS OF SIGNAL TRANSDUCTION AND GENE EXPRESSION IN HEPATOCELLULAR CARCINOMA

Abstract: 

Hepatocellular carcinoma (HCC) is the third deadliest form of cancer. Despite the progress that has been made, a significant knowledge gap in our understanding of the molecular mechanisms that underlie the development of HCC has not allowed the development of effective therapeutic, prognostic and diagnostic approaches.

The aim of the proposed project is the characterization of epigenetic and signal transduction mechanisms that deregulate the hepatic gene expression network in HCC. Moreover, it will exploit the scientific interdisciplinarity of the laboratories involved to extend the studies from cell and animal models to patient samples in order to improve our understanding of human HCC generation and progression and pave the way for the development of reliable prognostic and diagnostic protocols.

The project consists of five workpackages (WP):

  • WP1 will investigate the role of microRNAs in hepatic gene expression and its relationship to HCC.
  • WP2 will develop transgenic and knock-out mouse models to study the role of the histone methytranferase Smyd3 and the deubiquitinating enzyme CYLD in HCC. Smyd3 is overexpressed in HCC and affects hepatic gene expression by epigenetic mechanisms. CYLD is a tumor suppressor that is downregulated in HCC.
  • WP3 will investigate the mechanism of CYLD-mediated growth inhibition of HCC cells.
  • WP4 will establish a program for the management of the project and its resources.
  • WP5 will develop and implement a plan for the dissemination and exploitation of the results of the project.

It is anticipated that the proposed project with generate a wealth of novel information for our understanding of the pathogenesis of HCC. Novel mechanisms and molecules that are deregulated in HCC at multiple levels of cellular signal transduction will be uncovered and characterized. Our findings are expected to reveal novel target molecules for therapeutic intervention and allow the development of improved prognostic and diagnostic procedures.

Project info

Acronym:
STAGECAR
Coordinating Institution:
Aristotle University of Thessaloniki
Scientific Coordinator:
Mosialos George
Research Team 2 Leader:
Hadzopoulou-Cladaras Margarita
Research Team 3 Leader:
Talianidis Iannis

Stats

I.D.:
656
Mis:
379465
Duration (months):
47
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β4Λ59-ΘΨΩ

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