Study of the metabolism of fatty acids in cell proliferation and evaluation
of their potential use as a therapeutic target in cancer

Team of work

Principal InvestigatorScaglia

Scaglia, Natalia

Investigator
nscaglia@med.unlp.edu.ar

Borus, DelfinaBorus Delfina

Research Fellow
dborus@med.unlp.edu.ar

Costa, M. LucíaBorus Delfina

Research Fellow
lcosta@med.unlp.edu.ar

Collaborators from other institutions

Mancini, Estefanía
Centro de Regulación Genómica, Barcelona, España.

Zadra, Giorgia
Institute of Molecular Genetics, National Research Council, Pavia, Italy.

Line overview

Cancer cells engage in an increased de novo fatty acid synthesis as part of their anabolic reprogramming to support the active proliferation. Previous work from our and other groups has shown that fatty acid synthesis is essential for neoplastic cell proliferation and a putative therapeutic target for cancer treatment.
It is not known, however, why cancer cells rely on this anabolic route even in the presence of exogenous fatty acids. Additional evidence on the importance of de novo fatty acid synthesis for the division of normal mammalian cells and yeast suggests that it’s a general requirement for cellular proliferation. Normal cells, however, are less sensitive to the deleterious effect of the inhibition of this pathway than neoplastic cells, providing a therapeutic window for cancer treatment.

Our current work focuses on the channeling of fatty acids towards different metabolic fates. Particularly, we are studying the role of fatty acid binding proteins (FABP1 and 5) in colorectal and lung cancers.
Our main goal is to contribute to the understanding of the function and regulation of fatty acid and membrane phospholipid metabolism in cellular proliferation, and to apply this knowledge to test new therapeutic targets for cancer treatment and diagnosis.


Prostate Cancer Progression: as a Matter of Fats.
Scaglia, Natalia; Frontini-López, Yesica Romina; Zadra, Giorgia.
2021. Frontiers in oncology: Frontiers Media S.A. DOI: 10.3389/fonc.2021.719865

Fatty acid binding protein 5 regulates lipogenesis and tumor growth in lung adenocarcinoma.
García; Karina Andrea; Costa, María Lucía; Lacunza, Ezequiel; Martínez, María Elizabeth; Corsico, Betina; Scaglia, Natalia.
2020. ELSEVIER - Volume 301, 15 July 2022, 120621
doi.org/10.1016/j.lfs.2022.120621

De novo lipogénesis at the mitotic exit is used for nuclear envelope reassembly/expansion. Implications for combined chemotherapy.
Rodríguez Sawicki, Luciana; García, Karina A.; Córsico, Betina; Scaglia, Natalia.
2019: Cell cycle. Austin, Texas: LANDES BIOSCIENCE, p. 1646-1659. ISSN 1538-4101
doi.org/10.1080/15384101.2019.1629792

FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism.
Rodriguez Sawicki, L; Bottasso Arias, N. M; Scaglia, N; Falomir Lockhart, L; Franchini, G. R; Storch, J; Córsico, B.
2017. Biochimica et biophysica acta-molecular and cell biology of lipids. ELSEVIER SCIENCE BV. vol. 1862, n° 12, p. 1587-1594. ISSN 1388-1981

Analysis of triglyceride synthesis unveils a green algal soluble diacylglycerol acyltransferase and provides clues to potential enzymatic components of the chloroplast pathway.
Bagnato, C; Prados, M. B; Franchini, G. R; Scaglia, N; Miranda, S. E; Beligni, M. V.
2017. Bmc genomics: BIOMED CENTRAL LTD. vol. 18, n° 1, ISSN 1471-2164

A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis.
Zadra, G; Photopoulos, C; Tyekucheva, S; Heidari, P; Weng, Q. P; Fedele, G; Liu, H; Scaglia, N; Priolo, C; Sicinska, E; Mahmood, U; Signoretti, S; Birnberg, N; Loda, M.
2014. Embo Molecular Medicine. Londres: WILEY-BLACKWELL PUBLISHING, INC,. vol. 6, p. 519-538. ISSN 1757-4676

AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer.
. Priolo, C; Pyne, S; Rose, J; Regan, E. R; Zadra, G; Photopoulos, C; Cacciatore, S; Schulz, D; Scaglia, N; Mcdunn, J; De Marzo, A. M; Loda, M.
2014. Cancer Research. Philadelphia: AMER ASSOC CANCER RESEARCH,. vol. 74, n° 24, p. 7198-7204. ISSN 0008-5472

De novo fatty acid synthesis at the mitotic exit is required to complete cellular division.
Scaglia, N; Tyekucheva, S; Zadra, G; Photopoulos, C; Loda, M.
2014. Cell Cycle. Austin, Texas: LANDES BIOSCIENCE,. vol. 13, p. 859-868. ISSN 1538-4101

Inhibition of Stearoyl-CoA Desaturase 1 inactivates Acetyl-CoA Carboxylase and impairs proliferation in cancer cells: role of AMPK.
Scaglia, N; Chisholm, J. W; Igal, R. A.
2009. PLoS One. 4(8): e6812

Regulation of fatty acid synthesis and desaturation in senescence of human fibroblasts.
Maeda, M; Scaglia, N; Igal, R. A.
2009. Life Sci. 84:119-124

Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis.
Scaglia, N., Igal, R. A.
2008. Int J Oncol. 33(4):839-50

Stearoyl-CoA desaturase is involved in the control of proliferation, anchorage-independent growth, and survival in human transformed cells.
Scaglia, N; Igal, R. A.
2005. J Biol Chem. 280(27):25339-49

High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts.
Scaglia, N; Caviglia, J. M; Igal, R. A.
2005.Biochim Biophys Acta, 1687(1-3):141-51

Análisis estructural y funcional de macromoléculas.
Córsico, B; Falomir-Lockhart, L. J; Franchini, G. R; Scaglia, N.
2013. La Plata. Libro de Catedra. Edulp, p. 422. ISBN 978-950-34-1057-8
sedici.unlp.edu.ar/handle/10915/37269




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