Dlx-2 and glutaminase upregulate epithelial-mesenchymal transition and glycolytic switch

Su Yeon Lee; Hyun Min Jeon; Min Kyung Ju; Eui Kyong Jeong; Cho Hee Kim; Hye Gyeong Park; Song Iy Han; Ho Sung Kang

doi:10.18632/oncotarget.6879

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Dlx-2 and glutaminase upregulate epithelial-mesenchymal transition and glycolytic switch

Su Yeon Lee _, Hyun Min Jeon, Min Kyung Ju, Eui Kyong Jeong, Cho Hee Kim, Hye Gyeong Park, Song Iy Han and Ho Sung Kang

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2016; 7:7925-7939. https://doi.org/10.18632/oncotarget.6879

Metrics: PDF 3557 views | HTML 3323 views | ?

Abstract

Su Yeon Lee1, Hyun Min Jeon1, Min Kyung Ju1, Eui Kyong Jeong1, Cho Hee Kim1,*, Hye Gyeong Park2, Song Iy Han3, Ho Sung Kang1

1Department of Molecular Biology, College of Natural Sciences, Pusan 609-735, Korea

2Nanobiotechnology Center, Pusan National University, Pusan 609-735, Korea

3The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju 501-759, Korea

*Present address: DNA Identification Center, National Forensic Service, Seoul 158-707, Korea

Correspondence to:

Ho Sung Kang, e-mail: [email protected]

Keywords: Dlx-2, GLS1, Snail, epithelial-mesenchymal transition, glycolytic switch

Received: May 23, 2015 Accepted: January 02, 2016 Published: January 11, 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.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 6879

Publication Alerts

Research Papers:

Dlx-2 and glutaminase upregulate epithelial-mesenchymal transition and glycolytic switch

Abstract