| 1. |
- Ruiz-Pérez, María Victoria, et al.
(författare)
-
Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma
- 2021
-
Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 24:2
-
Tidskriftsartikel (refereegranskat)abstract
- Many metabolic pathways, including lipid metabolism, are rewired in tumors to support energy and biomass production and to allow adaptation to stressful environments. Neuroblastoma is the second deadliest solid tumor in children. Genetic aberrations, as the amplification of the MYCN-oncogene, correlate strongly with disease progression. Yet, there are only a few molecular targets successfully exploited in the clinic. Here we show that inhibition of fatty acid synthesis led to increased neural differentiation and reduced tumor burden in neuroblastoma xenograft experiments independently of MYCN-status. This was accompanied by reduced levels of the MYCN or c-MYC oncoproteins and activation of ERK signaling. Importantly, the expression levels of genes involved in de novo fatty acid synthesis showed prognostic value for neuroblastoma patients. Our findings demonstrate that inhibition of de novo fatty acid synthesis is a promising pharmacological intervention strategy for the treatment of neuroblastoma independently of MYCN-status.
|
|
| 2. |
- Sainero-Alcolado, Lourdes, et al.
(författare)
-
Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma
- 2024
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 121:7, s. 2310479121-2310479121
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.
|
|
| 3. |
|
|
| 4. |
- Tchebakova, N. M., et al.
(författare)
-
Energy and Mass Exchange and the Productivity of Main Siberian Ecosystems (from Eddy Covariance Measurements). 2. Carbon Exchange and Productivity
- 2015
-
Ingår i: Biology Bulletin of the Russian Academy of Science. - 1062-3590. ; 42:6, s. 579-588
-
Tidskriftsartikel (refereegranskat)abstract
- Direct measurements of CO2 fluxes by the eddy covariance method have demonstrated that the examined middle-taiga pine forest, raised bog, true steppe, and southern tundra along the Yenisei meridian (similar to 90 degrees E) are carbon sinks of different capacities according to annual output. The tundra acts as a carbon sink starting from June; forest and bog, from May; and steppe, from the end of April. In transitional seasons and winter, the ecosystems are a weak source of carbon; this commences from September in the tundra, from October in the forest and bog, and from November in the steppe. The photosynthetic productivity of forest and steppe ecosystems, amounting to 480-530 g C/(m(2) year), exceeds by 2-2.5 times that of bogs and tundras, 200-220 g C/(m(2) year). The relationships between the heat balance structure and CO2 exchange are shown. Possible feedback of carbon exchange between the ecosystems and atmosphere as a result of climate warming in the region are assessed.
|
|
