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Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids [PS-ac-peptide]

ABSTRACT: Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids [PS-ac-peptide]

PROVIDER: PRJNA828157 | ENA |

REPOSITORIES: ENA

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Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids [PS-ac-peptide]

Project description:Overcoming resistance to chemotherapies remains a major unmet need for cancers such as triple negative breast cancer (TNBC). Therefore, mechanistic studies to provide insight for drug development are urgently needed to overcome TNBC therapy resistance. Recently, an important role of fatty acid β-Oxidation (FAO) in chemoresistance has been shown. But how FAO might mitigate tumor cell apoptosis by chemotherapy is unclearknown. Here, we show that elevated FAO activates STAT3 by acetylation via elevated acetyl-CoA. Acetylated STAT3 upregulates expression of long-chain acyl-CoA synthetase 4 (ACSL4), resulting in increased phospholipid synthesis. Elevating phospholipids in mitochondrial membranes leads to heightened mitochondrial integrity, which in turn overcomes chemotherapy-induced tumor cell apoptosis. Conversely, in both cultured tumor cells and xenograft tumors, enhanced cancer cell apoptosis by inhibiting ASCL4 or specifically targeting acetylated-STAT3 is associated with a reduction in phospholipids within mitochondrial membranes. This study demonstrates a critical mechanism underlying tumor cell chemoresistance.

2022-05-31 | GSE201052 | GEO

Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids

Project description:Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids

| PRJNA828154 | ENA

Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids [STAT3]

Project description:Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids [STAT3]

| PRJNA828158 | ENA

Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-05-31 | GSE201053 | GEO

Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids [STAT3]

2022-05-31 | GSE201051 | GEO

PE and PS Lipids Synergistically Enhance Membrane Poration by a Peptide with Anticancer Properties.

Project description:Polybia-MP1 (MP1) is a bioactive host-defense peptide with known anticancer properties. Its activity is attributed to excess serine (phosphatidylserine (PS)) on the outer leaflet of cancer cells. Recently, higher quantities of phosphatidylethanolamine (PE) were also found at these cells' surface. We investigate the interaction of MP1 with model membranes in the presence and absence of POPS (PS) and DOPE (PE) to understand the role of lipid composition in MP1's anticancer characteristics. Indeed we find that PS lipids significantly enhance the bound concentration of peptide on the membrane by a factor of 7-8. However, through a combination of membrane permeability assays and imaging techniques we find that PE significantly increases the susceptibility of the membrane to disruption by these peptides and causes an order-of-magnitude increase in membrane permeability by facilitating the formation of larger transmembrane pores. Significantly, atomic-force microscopy imaging reveals differences in the pore formation mechanism with and without the presence of PE. Therefore, PS and PE lipids synergistically combine to enhance membrane poration by MP1, implying that the combined enrichment of both these lipids in the outer leaflet of cancer cells is highly significant for MP1's anticancer action. These mechanistic insights could aid development of novel chemotherapeutics that target pathological changes in the lipid composition of cancerous cells.

| S-EPMC4564682 | biostudies-literature

Azospira oryzae PS strain:PS

Project description:Azospira oryzae PS strain:PS Genome sequencing

| PRJNA250450 | ENA

Sphaerochaeta sp. PS strain:PS

Project description:Sphaerochaeta sp. PS strain:PS Genome sequencing and assembly

| PRJNA1019525 | ENA

Biosynthesis of membrane-spanning lipids in Thermoanaerobacter ethanolicus

Project description:This study was conducted to identify the genes involved in the synthesis of membrane-spanning lipids in Thermoanaerobacter ethanolicus JW 200.

2022-10-26 | GSE211546 | GEO

Biosynthesis of membrane-spanning ether lipids in Thermotoga maritima

Project description:This study was conducted to identify the genes involved in the synthesis of membrane-spanning ether lipids in Thermotoga maritima MSB8.

2022-10-26 | GSE211547 | GEO

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