Research Papers:

Targeting a novel cancer-driving protein (LAPTM4B-35) by a small molecule (ETS) to inhibit cancer growth and metastasis

Maojin Li _, Rouli Zhou, Yi Shan, Li Li, Lin Wang and Gang Liu

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Oncotarget. 2016; 7:58531-58542. https://doi.org/10.18632/oncotarget.11325

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Maojin Li1, Rouli Zhou1, Yi Shan1, Li Li3, Lin Wang3, Gang Liu2

1Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing 100191, China

2School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, P.R. China

3Department of Synthetic Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Correspondence to:

Rouli Zhou, email: [email protected]

Gang Liu, email: [email protected]

Keywords: LAPTM4B-35, ethylglyoxal bisthiosemicarbazon (ETS), hepatocellular-carcinoma, cancer targeted therapy, apoptosis

Received: March 05, 2016    Accepted: July 18, 2016    Published: August 17, 2016


Our previous studies demonstrated that LAPTM4B-35 is overexpressed in a variety of solid cancers including hepatocellular carcinoma (HCC), and is an independent factor for prognosis. LAPTM4B-35 overexpression causes carcinogenesis and enhances cancer growth, metastasis and multidrug resistance, and thus may be a candidate for therapeutic targeting. The present study shows ethylglyoxal bisthiosemicarbazon (ETS) has effective anticancer activity through LAPTM4B-35 targeting. Bel-7402 and HepG2 cell lines from human HCC were used as cell models in which LAPTM4B-35 is highly expressed, and a human fetal liver cell line was used as a control. The results showed ETS has a specific and pronounced lethal effect on HCC cells, but not on fetal liver cells in culture. ETS also attenuated growth and metastasis of human HCC xenograft in nude mice, and extended the life span of mice with HCC. ETS induced HCC cell apoptosis, and upregulated a large number of proapoptotic genes and downregulated antiapoptotic genes. When endogenous overexpression of LAPTM4B-35 was knocked down with RNAi, the killing effect of ETS on HepG2 cells was significantly attenuated. ETS also inhibited phosphorylation of LAPTM4B-35 Tyr285, which involves in activation of the PI3K/Akt signaling pathway induced by LAPTM4B-35 overexpression. In addition, the induction of alterations in quantity of c-Myc, Bcl-2, Bax, cyclinD1 and Akt-p molecules in HepG2 cells by LAPTM4B-35 overexpression could be reversed by ETS. Conclusion: ETS is a promising candidate for treatment of HCC through LAPTM4B-35 protein targeting.

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