Back to Search
Start Over
LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma
- Source :
- Cell Death and Disease, Vol 12, Iss 9, Pp 1-14 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Tumor cells require high levels of cholesterol for membrane biogenesis for rapid proliferation during development. Beyond the acquired cholesterol from low-density lipoprotein (LDL) taken up from circulation, tumor cells can also biosynthesize cholesterol. The molecular mechanism underlying cholesterol anabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are unclear. Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we identified that LPCAT1 is highly expressed in ESCC and that LPCAT1 reprograms cholesterol metabolism in ESCC. LPCAT1 expression was negatively correlated with patient prognosis. Cholesterol synthesis in ESCC cells was significantly inhibited following LPCAT1 knockdown; cell proliferation, invasion, and migration were significantly reduced, along with the growth of xenograft subcutaneous tumors. LPCAT1 could regulate the expression of the cholesterol synthesis enzyme, SQLE, by promoting the activation of PI3K, thereby regulating the entry of SP1/SREBPF2 into the nucleus. LPCAT1 also activates EGFR leading to the downregulation of INSIG-1 expression, facilitating the entry of SREBP-1 into the nucleus to promote cholesterol synthesis. Taken together, LPCAT1 reprograms tumor cell cholesterol metabolism in ESCC and can be used as a potential treatment target against ESCC.
- Subjects :
- Male
Cancer Research
Esophageal Neoplasms
Transcription, Genetic
Apoptosis
Mice, SCID
chemistry.chemical_compound
Cell Movement
Mice, Inbred NOD
Medicine
Cell Cycle
1-Acylglycerophosphocholine O-Acyltransferase
Middle Aged
Prognosis
Neoplasm Proteins
Up-Regulation
Gene Expression Regulation, Neoplastic
Cholesterol
Disease Progression
Female
lipids (amino acids, peptides, and proteins)
Esophageal Squamous Cell Carcinoma
Signal Transduction
Immunology
Cellular and Molecular Neuroscience
Downregulation and upregulation
Cell Line, Tumor
Lysophosphatidylcholine acyltransferase 1
Animals
Humans
Neoplasm Invasiveness
PI3K/AKT/mTOR pathway
Cell Proliferation
Base Sequence
QH573-671
business.industry
Cell growth
Cancer
Lipid metabolism
Cell Biology
medicine.disease
Anoikis
digestive system diseases
chemistry
Membrane biogenesis
Cancer research
business
Cytology
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....b8099230b8eb9d206e594b7c0abe7c3b