Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 455, Issue 3-4, Pages 153-158Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.10.129
Keywords
alpha Pix; c-Cbl; Cell migration; Cell invasion; Glioma
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Funding
- National Research Foundation of Korea [NRF-2005-084-C00025, M10533010001-05N3301]
- National Research Foundation of Korea [2005-084-C00025] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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c-Cbl, a RING-type ubiquitin E3 ligase, down-regulates receptor tyrosine kinases, including EGF receptor, and inhibits cell proliferation. Moreover, c-Cbl mutations are frequently found in patients with myeloid neoplasm. Therefore, c-Cbl is known as a tumor suppressor. alpha Pix is expressed only in highly proliferative and mobile cells, including immune cells, and up-regulated in certain invasive tumors, such as glioblastoma multiforme. Here, we showed that c-Cbl serves as an ubiquitin E3 ligase for proteasome-mediated degradation of alpha Pix, but not beta Pix. Remarkably, the rat C6 and human A172 glioma cells were unable to express c-Cbl, which leads to a dramatic accumulation of alpha Pix. Depletion of alpha Pix by shRNA markedly reduced the ability of the glioma cells to migrate and invade, whereas complementation of shRNA-insensitive alpha Pix promoted it. These results indicate that c-Cbl negatively regulates alpha Pix-mediated cell migration and invasion and the lack of c-Cbl in the C6 and A172 glioma cells is responsible for their malignant behavior. (C) 2014 Elsevier Inc. All rights reserved.
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