scholarly journals Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer

2020 ◽  
Vol 696 ◽  
pp. 108664
Author(s):  
Liqiang Wang ◽  
Changfeng Li ◽  
Yumei Song ◽  
ZhenKun Yan
Oncogene ◽  
2019 ◽  
Vol 38 (23) ◽  
pp. 4637-4654 ◽  
Author(s):  
Wanming He ◽  
Bishan Liang ◽  
Chunlin Wang ◽  
Shaowei Li ◽  
Yang Zhao ◽  
...  

2020 ◽  
Author(s):  
Liqiang Wang ◽  
Changfeng Li ◽  
Yumei Song ◽  
ZhenKun Yan

Abstract Background: Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyltransferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified unclear. Methods: To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro . Results: Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell FAO via increasing NADP + /NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration. Conclusion: Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC. Keywords: CPT1A; gastric cancer; fatty acid oxidation; prognostic; progression


2003 ◽  
Vol 54 (4) ◽  
pp. 446-451 ◽  
Author(s):  
Fatima Djouadi ◽  
Jean-Paul Bonnefont ◽  
Laure Thuillier ◽  
Véronique Droin ◽  
Noman Khadom ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jae-Seon Lee ◽  
Seung Hwa Kim ◽  
Soohyun Lee ◽  
Joon Hee Kang ◽  
Seon-Hyeong Lee ◽  
...  

Abstract The major source of ATP in cancer cells remains unclear. Here, we examined energy metabolism in gastric cancer cells and found increased fatty acid oxidation and increased expression of ALDH3A1. Metabolic analysis showed that lipid peroxidation by reactive oxygen species led to spontaneous production of 4-hydroxynonenal, which was converted to fatty acids with NADH production by ALDH3A1, resulting in further fatty acid oxidation. Inhibition of ALDH3A1 by knock down using siRNA of ALDH3A1 resulted in significantly reduced ATP production by cancer cells, leading to apoptosis. Oxidative phosphorylation by mitochondria in gastric cancer cells was driven by NADH supplied via fatty acid oxidation. Therefore, blockade of ALDH3A1 together with mitochondrial complex I using gossypol and phenformin led to significant therapeutic effects in a preclinical gastric cancer model.


2019 ◽  
Author(s):  
Jae-Seon Lee ◽  
Seung Hwa Kim ◽  
Soohyun Lee ◽  
Joon Hee Kang ◽  
Seon-Hyeong Lee ◽  
...  

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