title: Lamp2a is required for tumor growth and promotes tumor recurrence of hepatocellular carcinoma.
abstract: Exploring the function of chaperone-mediated autophagy (CMA) in cancer has promoted progress in cancer treatment through the regulation of CMA pathways. However, CMA status and function in hepatocellular carcinoma (HCC) by focusing on the regulatory role of lyso-some-associated membrane protein type 2a (Lamp2a) remain to be clarified. We examined Lamp2a in a normal human liver cell line, 6 HCC cell lines, 10 normal liver samples as well as 42 HCC tissue and para-tumor tissues samples, and then validated it in 228 HCC patients to assess the relationship between Lamp2a and clinical prognosis. Gain and loss of Lamp2a function were also explored in HCC cell lines and xenograft models. Significantly lower level of Lamp2a expression was found in HCC cells and tissues compared with normal hepatic cells, para-tumor tissues and normal livers. Although no differences in HCC cell morphology or function were observed in relation to Lamp2a expression under normal culture or short-term starvation conditions, Lamp2a blockage significantly inhibited HCC cell viability under prolonged starvation. Critically, Lamp2a is required for HCC xenograft growth in vivo by helping cells to avoid apoptosis and promoting cell proliferation. Furthermore, a significant correlation between Lamp2a expression and tumor size or cumulative recurrence was uncovered in HCC patients. Collectively, the present study shows that impaired Lamp2a expression in HCC contributes to tumor cell viability and promotes tumor growth and recurrence. Targeting chaperone-mediated autophagy through Lamp2a may also imply a potentially novel treatment strategy for HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhen-Bin
authors.initials: ZB
authors.lastname: Ding
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xiu-Tao
authors.initials: XT
authors.lastname: Fu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Yuan-Fei
authors.initials: YF
authors.lastname: Peng
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Liu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Song
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Meng-Xin
authors.initials: MX
authors.lastname: Tian
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Shen
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D056945:Hep G2 Cells; D064593:Heterografts / Q000254:growth & development*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D034741:RNA, Small Interfering