LAPTM4B facilitates tumor growth and induces autophagy in hepatocellular carcinoma

Fei Wang,1,2 Huita Wu,3 Sheng Zhang,4 Jing Lu,1 Yuyan Lu,1 Ping Zhan,1 Qinliang Fang,1 Fuqiang Wang,1 Xiuming Zhang,5 Chengrong Xie,1 Zhenyu Yin11Department of Hepatobiliary Surgery, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Oncology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 5Department of Biomaterials, College of Materials, Xiamen University, Xiamen, Fujian, People’s Republic of ChinaBackground: 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.Keywords: autophagy, apoptosis, LAPTM4B, ATG3