Confirmation and functional analysis of the interaction of new proteins that interact with the cytoplasmic region of CD30 the marker protein for Hodgin lymphoma

• Grant number: 11/20086-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2012
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Bruno Aquino
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Normal cells generate high amounts of ATP by metabolizing glucose completely to carbon dioxide. In contrast, rapidly growing cancer cells restrict this metabolic pathway and profit from intermediate products for the biosynthesis of cell components and to influence the microenvironment. The lower molar ATP yield is compensated by increased glucose consumption. This metabolic switch is critically regulated by the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1). Its overexpression stimu-lates the glucose turnover and even immortalizes non-malignant cells. PGAM1 is generally controlled by the tumor suppressor p53 but functional p53 defects in many tumors allow PGAM1-dependent survival signaling. However, small molecule PGAM1 inhibitors are able to suppress cell growth, instead. Searching for p53-independent mechanisms to curb tumor cell glycolysis, we found that the receptor CD30 directly interacts with PGAM1. CD30 is selectively expressed on the malignant cells of anaplastic large cell lymphoma (ALCL) and agonistic stimulation of CD30 reduced glucose uptake and cell viability. In this project, we will test the hypothesis that the CD30-dependent loss of cell viability is due to a direct inhibition of the abnormal tumor cell glycolysis. Understanding this so far unknown signaling pathway and its impact on the glucose uptake and metabolome in tumor cells might provide new therapeutic options to damage cancer cells by limiting its deregulated glucose metabolism.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREZ, ARINA MARINA; AQUINO, BRUNO; VIVIANI, VADIM; KOBARG, JORG. Use of a special Brazilian red-light emitting railroad worm Luciferase in bioassays of NEK7 protein Kinase and Creatine Kinase. BMC BIOCHEMISTRY, v. 18, JUL 19 2017. (11/20086-1, 13/09594-0, 14/21700-3, 12/22265-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AQUINO, Bruno. Confirmation and functional analysis of new interacting proteins that interacts with the intracellular region of the Hodgkin lymphoma marker CD30. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.