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学科主题: 基础医学
题名:
LAPTM4B: A novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling
作者: Li, L.; Wei, X. H.; Pan, Y. P.; Li, H. C.; Yang, H.; He, Q. H.; Pang, Y.; Shan, Y.; Xiong, F. X.; Shao, G. Z.; Zhou, R. L.
关键词: LAPTM4B ; multidrug resistance ; drug efflux ; PI3K-AKT signaling
刊名: ONCOGENE
发表日期: 2010-10-01
DOI: 10.1038/onc.2010.303
卷: 29, 期:43, 页:5785-5795
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]: HEPATOCELLULAR-CARCINOMA ; P-GLYCOPROTEIN ; DRUG-RESISTANCE ; TETRATRANSMEMBRANE PROTEIN ; SACCHAROMYCES-CEREVISIAE ; MEMBRANE-PROTEIN ; CELLS ; EXPRESSION ; OVEREXPRESSION ; PROGRESSION
英文摘要:

LAPTM4B (lysosomal protein transmembrane 4 beta) is a newly identified cancer-associated gene. Both of its mRNA and the encoded LAPTM4B-35 protein are significantly upregulated with more than 70% frequency in a wide variety of cancers. The LAPTM4B-35 level in cancer is evidenced to be an independent prognostic factor and its upregulation promotes cell proliferation, migration and invasion, as well as tumorigenesis in nude mice. In contrary, knockdown of LAPTM4B-35 expression by RNA interference (RNAi) reverses all of the above malignant phenotypes. We herein reveal a new role of LAPTM4B-35 in promoting multidrug resistance of cancer cells. Upregulation of LAPTM4B-35 motivates multidrug resistance by enhancement of efflux from cancer cells of a variety of chemodrugs with variant structures and properties, including doxorubicin, paclitaxel and cisplatin through colocalization and interaction of LAPTM4B-35 with multidrug resistance (MDR) 1 (P-glycoprotein, P-gp), and also by activation of PI3K/AKT signaling pathway through interaction of PPRP motif contained in the N-terminus of LAPTM4B-35 with the p85 alpha regulatory subunit of PI3K. The specific inhibitors of PI3K and knockdown of LAPTM4B-35 expression by RNAi eliminate the multidrug resistance effect motivated by upregulation of LAPTM4B-35. In conclusion, LAPTM4B-35 motivates multidrug resistance of cancer cells by promoting drug efflux through colocalization and interaction with P-gp, and anti-apoptosis by activating PI3K/AKT signaling. These findings provide a promising novel strategy for sensitizing chemical therapy of cancers and increasing the chemotherapeutic efficacy through knockdown LAPTM4B-35 expression by RNAi. Oncogene (2010) 29, 5785-5795; doi: 10.1038/onc.2010.303; published online 16 August 2010

语种: 英语
所属项目编号: 2006AA02A305 ; H020220020310 ; 90408018
项目资助者: 211 and 985 Foundation of Peking University ; National High-tech R&amp ; D Program (863 Program) ; 248 major R&amp ; D program of Beijing ; NNSFC
WOS记录号: WOS:000283586200004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55387
Appears in Collections:基础医学院_细胞生物学系_期刊论文

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作者单位: Peking Univ, Sch Basic Med Sci, Dept Cell Biol, Beijing 100191, Peoples R China

Recommended Citation:
Li, L.,Wei, X. H.,Pan, Y. P.,et al. LAPTM4B: A novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling[J]. ONCOGENE,2010,29(43):5785-5795.
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