Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells.
We have previously reported the presence of Dlxin-1, a member of the melanoma antigen gene (MAGE) family, in the brain and showed its function as a cell cycle arrest protein, suggesting that Dlxin-1 may have anti-proliferative functions in rapidly growing tumors. Using the cancer stem cell hypothesis, which attributes the initiation and progression of brain tumors to the cancer-initiating stem cells, we have investigated the role of Dlxin-1 in the glioma stem cells propagated by us as a cell culture system comprising of HNGC-2 cells. Our studies provide evidence about the role of Dlxin-1 as an anti-tumorigenic protein in the highly chemo-resistant glioma stem cells. Next, we show that these anti-proliferative effects are manifested by Dlxin-1 through down regulation of the activities of MMP-2 and MMP-9, and through interaction of Dlxin-1 with its target protein P311 that is involved in glioma cell invasion. In summary, we establish the roles for Dlxin-1, one as an anti-tumorigenic and anti-invasive protein in high-grade gliomas and the other as an inducer of differentiation of glioma stem cells. These two attributes, in conjunction, result in conversion of the drug-resistant brain tumor stem cells to the tumor-attenuated cells that may now be more amenable to effective therapeutic targeting.
National Centre for Cell Science, NCCS Complex, University of Pune Campus, Pune, Maharashtra, India.
E M
EM
Reddy
S T
ST
Chettiar
N
N
Kaur
R
R
Ganeshkumar
V
V
Shepal
N C
NC
Shanbhag
A
A
Shiras
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D058950:Melanoma-Specific Antigens / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
D050759:Cyclin-Dependent Kinase Inhibitor p21; D058950:Melanoma-Specific Antigens; C428027:NREP protein, human; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D020778:Matrix Metalloproteinase 2