Energetic metabolism study on melanoma progression based on mitochondrial genome instability

• Grant number: 13/25119-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2014
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Wilson Araújo da Silva Junior
• Grantee: Luíza Ferreira de Araújo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID
• Associated scholarship(s): 15/21940-7 - Examination of Mitochondrial DNA Instability in Melanoma Tumorigenesis and Metastasis, BE.EP.DR

Abstract

Melanoma causes the majority of deaths related to skin cancer. This cancer follows a classic progression, which is subdivided on the basis of cellular penetration. In invasive cancers, metabolic reprogramming is associated with the physiopathology of neoplastic cells. Metabolic reprogramming affects ATP production by the down-regulation of OXPHOS, which happens in the inner mitochondrial membrane. Many studies have shown that tumor cells-metabolic reprogramming is triggered by ROS production, which is generated by mitochondrial complexes and critical for HIF1± stabilization. Furthermore, ROS damages mtDNA and those mutations were associated with development of a metastatic potential. Little is known about mtDNA variations and their consequences on tumorigenesis. Previous results from our group have shown increased mitochondrial genome instability in colorectal adenoma and adenocarcinoma. Interestingly, different genic mitochondrial complexes were affected in each tissue, which suggests distinct roles of the mitochondrial complexes on colorectal tumorigenesis. Melanoma cell lines from different stages of progression (Radial Growth Phase, Vertical Growth Phase and Metastatic Melanoma) are excellent experimental models to evaluate the mitochondrial genome instability and their consequences on energetic metabolism alteration. Taken together, the main goal of this study is to investigate if the mitochondrial genome instability promotes metabolic reprograming on Melanoma progression. (AU)

Scientific publications

(4)

(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)

MUYS, BRUNA RODRIGUES; SOUSA, JOSANE F.; PLACA, JESSICA RODRIGUES; DE ARAUJO, LUIZA FERREIRA; SARSHAD, AISHE A.; ANASTASAKIS, DIMITRIOS G.; WANG, XIANTAO; LI, XIAO LING; DE MOLFETTA, GREICE ANDREOTTI; RAMAO, ANELISA; et al. miR-450a Acts as a Tumor Suppressor in Ovarian Cancer by Regulating Energy Metabolism. Cancer Research, v. 79, n. 13, p. 3294-3305, JUL 1 2019. (16/22307-9, 13/08135-2, 09/53853-5, 13/25119-0, 13/25326-6)

ARAUJO, L. F.; TERRA, JR., A. T.; SARES, C. T. G.; SOBREIRA, C. F. R.; FARIA, E. F.; MACHADO, R. D.; RODRIGUES, JR., A. A.; MUGLIA, V. F.; SILVA, JR., W. A.; REIS, R. B.. Mitochondrial genome analysis in penile carcinoma. MOLECULAR BIOLOGY REPORTS, v. 45, n. 4, p. 591-600, AUG 2018. (13/08135-2, 09/53853-5, 13/25119-0)

ARAUJO, LUIZA FERREIRA; MOLFETTA, GREICE ANDREOTTI; VINCENZI, OTAVIO COSTA; HUBER, JAIR; TEIXEIRA, LORENA ALVES; FERRAZ, VICTOR EVANGELISTA; SILVA JR, WILSON ARAUJO. Molecular basis of familial adenomatous polyposis in the southeast of Brazil: identification of six novel mutations. International Journal of Biological Markers, v. 34, n. 1, p. 80-89, MAR 2019. (13/08135-2, 09/53853-5, 11/11456-0, 13/25119-0)

ARAUJO, L. F.; SIENA, A. D. D.; PLACA, J. R.; BROTTO, D. B.; BARROS, I. I.; MUYS, B. R.; BIAGI JR, C. A. O.; PERONNI, K. C.; SOUSA, J. F.; MOLFETTA, G. A.; et al. Mitochondrial transcription factor A (TFAM) shapes metabolic and invasion gene signatures in melanoma. SCIENTIFIC REPORTS, v. 8, SEP 21 2018. (18/04017-9, 13/08135-2, 09/53853-5, 15/21940-7, 13/25119-0)

Academic Publications

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

ARAÚJO, Luíza Ferreira de. Energetic metabolism analysis based on the instability of the mitochondrial genome in melanoma. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.