EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

Journal Article · Fri May 02 00:00:00 EDT 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2014.03.127· OSTI ID:22416410

Huang, Er-Wen ^[1]; Xue, Sheng-Jiang ^[2]; Li, Xiao-Yan ^[3]; Xu, Suo-Wen ^[4]; Cheng, Jian-Ding; Zheng, Jin-Xiang ^[2]; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong ^[1]; Li, Jie ^[5]; Liu, Chao ^[1]

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1. Guangzhou Institute of Forensic Science, Guangzhou (China)
2. Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China)
3. Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)
4. Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China)
5. Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China)

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

• OSTI ID: 22416410
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 447, Issue 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BONE MARROW
CELL CYCLE
CELL PROLIFERATION
GROWTH FACTORS
INSULIN
MITOCHONDRIA
MOLECULES
PHENOTYPE
PHOSPHOTRANSFERASES
PLASMA CELLS
SECRETION