LAPTM4B facilitates tumor growth and induces autophagy in hepatocellular carcinoma
LAPTM4B facilitates tumor growth and induces autophagy in hepatocellular carcinoma
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LAPTM4B 促进肝细胞癌中的肿瘤生长并诱导自噬
DOI：
10.2147/cmar.s201092
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发表时间：
2019
影响因子：
3.3
通讯作者：
Yin Zhenyu
中科院分区：
文献类型：
--
作者：
Wang Fei;Wu Huita;Zhang Sheng;Lu Jing;Lu Yuyan;Zhan Ping;Fang Qinliang;Wang Fuqiang;Zhang Xiuming;Xie Chengrong;Yin Zhenyu
背景：肝细胞癌（HCC）是最常见的癌症之一，也是癌症相关死亡的第三大原因。据报道，溶酶体相关跨膜蛋白LAPTM4B表达在人类癌症中显著上调，并且与肿瘤的发生和进展密切相关。目的：探讨LAPTM 4B与肝癌发病机制的关系。研究方法：采用细胞活力测定、集落形成试验、体内异种移植模型、芯片、实时荧光定量PCR、免疫荧光和Western印迹分析等方法。结果：LAPTM 4B在体外可促进肝癌细胞增殖，在体内可促进肝癌的发生。此外，在饥饿条件下，LAPTM 4B促进细胞存活、抑制细胞凋亡并诱导自噬通量。表达谱分析结合基因本体（GO）分析显示，LAPTM4B沉默下调的159个基因在响应营养和一些代谢过程中显着富集。此外，LAPTM4B激活ATG 3转录以调节HCC细胞凋亡和自噬。结论：我们的研究结果表明，LAPTM4B作为一个癌基因，促进肝癌的肿瘤发生和自噬，并表明LAPTM4B可能被用作肝癌治疗的新的治疗靶点。
Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the third leading cause of cancer-related deaths. It has been reported that lysosomal associated transmembrane protein LAPTM4B expression is significantly upregulated in human cancers and closely associated with tumor initiation and progression. Purpose: We aimed to reveal the relevance of LAPTM4B and the pathogenesis of HCC. Methods: Cell viability assessment, colony formation assay, in vivo xenograrft model, microarray, real-time PCR, immunofluorescence and western blot analysis were applied. Results: Our results demonstrated that LAPTM4B promoted HCC cell proliferation in vitro and tumorigenesis in vivo. Additionally, upon starvation conditions, LAPTM4B facilitated cell survival, inhibited apoptosis and induced autophagic flux. Expression profiling coupled with gene ontology (GO) analysis revealed that 159 gene downregulated by LAPTM4B silencing was significantly enriched in response to nutrient and some metabolic processes. Moreover, LAPTM4B activated ATG3 transcription to modulate HCC cell apoptosis and autophagy. Conclusion: Our findings demonstrate that LAPTM4B acts as an oncogene that promotes HCC tumorigenesis and autophagy, and indicate that LAPTM4B may be used as a novel therapeutic target for HCC treatment.