肉毒碱棕榈酰基转移酶 1A 诱导的脂肪酸氧化抑制抑制胃癌细胞进展。

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

机构信息

Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, China.

Department of Thoracic Oncology, Tumor Hospital of Jilin Province, Changchun, Jilin Province, 130033, China.

出版信息

Arch Biochem Biophys. 2020 Dec 15;696:108664. doi: 10.1016/j.abb.2020.108664. Epub 2020 Nov 4.

DOI:10.1016/j.abb.2020.108664

PMID:33157102

Abstract

BACKGROUND

Gastric 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.

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 fatty acid oxidation (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.

摘要

背景

胃癌（GC）转移率高，是导致死亡的主要原因。肉毒碱棕榈酰转移酶 1a（CPT1A）已被报道在各种类型的癌症进展中起着关键的障碍作用，这是癌症治疗的一个有吸引力的焦点。然而，CPT1A 参与 GC 的潜在分子机制尚不清楚。

方法

确定 CPT1A 在人 GC 组织和细胞中的表达，并阐明其是否与 GC 患者的临床病理特征和预后相关。通过体外敲低/过表达 GC 细胞中的 CPT1A 来评估其在调节肿瘤生长和侵袭中的作用及其潜在机制。

结果

CPT1A 蛋白表达在 GC 细胞和组织中明显上调，与 GC 患者的分级、病理分期、淋巴结转移和预后不良相关。CPT1A 过表达也促进了 GC 细胞的增殖、侵袭和 EMT 过程。此外，CPT1A 的上调通过增加 NADP/NADPH 比值激活 GC 细胞脂肪酸氧化（FAO），而 FAO 的抑制则消除了 CPT1A 对 GC 细胞增殖和迁移的影响。