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| Content Provider | PubMed Central |
|---|---|
| Author | Lee, Su Yeon Jeon, Hyun Min Kyung, Ju Min Jeong, Eui Kyong Kim, Cho Hee Park, Hye Gyeong Han, Song Iy Kang, Ho Sung |
| Copyright Year | 2016 |
| Abstract | Most cancer cells depend on enhanced glucose and glutamine (Gln) metabolism for growth and survival. Oncogenic metabolism provides biosynthetic precursors for nucleotides, lipids, and amino acids; however, its specific roles in tumor progression are largely unknown. We previously showed that distal-less homeobox-2 (Dlx-2), a homeodomain transcription factor involved in embryonic and tumor development, induces glycolytic switch and epithelial-mesenchymal transition (EMT) by inducing Snail expression. Here we show that Dlx-2 also induces the expression of the crucial Gln metabolism enzyme glutaminase (GLS1), which converts Gln to glutamate. TGF-β and Wnt induced GLS1 expression in a Dlx-2-dependent manner. GLS1 shRNA (shGLS1) suppressed in vivo tumor metastasis and growth. Inhibition of Gln metabolism by shGLS1, Gln deprivation, and Gln metabolism inhibitors (DON, 968 and BPTES) prevented Dlx-2-, TGF-β-, Wnt-, and Snail-induced EMT and glycolytic switch. Finally, shDlx-2 and Gln metabolism inhibition decreased Snail mRNA levels through p53-dependent upregulation of Snail-targeting microRNAs. These results demonstrate that the Dlx-2/GLS1/Gln metabolism axis is an important regulator of TGF-β/Wnt-induced, Snail-dependent EMT, metastasis, and glycolytic switch. |
| Related Links | http://dx.doi.org/10.18632/oncotarget.6879 |
| Ending Page | 7939 |
| Page Count | 15 |
| Starting Page | 7925 |
| File Format | |
| ISSN | 19492553 |
| e-ISSN | 19492553 |
| Journal | Oncotarget |
| Issue Number | 7 |
| Volume Number | 7 |
| Language | English |
| Publisher | Impact Journals LLC |
| Publisher Date | 2016-02-01 |
| Access Restriction | Open |
| Rights Holder | Impact Journals LLC |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
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