Abstract
BackgroundGastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyl transferase 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 clear. MethodsTo 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. ResultsMarked 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 fatty acid oxidation (FAO) via increasing NADP+/NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration. ConclusionOur 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.
Highlights
Gastric cancer (GC) is a common malignancy and has the highest incidence and mortality in the digestive tract [1]
Carnitine palmitoyltransferase 1a (CPT1A) is highly expressed in GC cell lines and tumor tissues To investigate the role of CPT1A in the development of GC, we discovered that
CPT1A was markedly increased in GC tissues from the Cancer Genome Atlas (TCGA) database and GEPIA datasets (Fig. 1a and 1b)
Summary
Gastric cancer (GC) is a common malignancy and has the highest incidence and mortality in the digestive tract [1]. The reprogramming of cellular energy metabolism, which support the unrestricted proliferation and metastatic progression of cancer cells, is widely accepted to be an emerging hallmark of cancer [7,8,9]. Wang et al reported that CPT1A-induced FAO activation increased metastatic ability [16]. These findings reveals that inhibiting FAO might be the potential of strategy in cancer therapy. 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. 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.
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