SOX9-PDK1 axis is essential for glioma stem cell self-renewal and temozolomide resistance

Zhen Wang; Xiaoshan Xu; Nan Liu; Yingduan Cheng; Weilin Jin; Pengxing Zhang; Xin Wang; Hongwei Yang; Hui Liu; Yanyang Tu

doi:10.18632/oncotarget.22773

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:

SOX9-PDK1 axis is essential for glioma stem cell self-renewal and temozolomide resistance

Zhen Wang, Xiaoshan Xu, Nan Liu, Yingduan Cheng, Weilin Jin, Pengxing Zhang, Xin Wang, Hongwei Yang, Hui Liu and Yanyang Tu _

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2018; 9:192-204. https://doi.org/10.18632/oncotarget.22773

Metrics: PDF 1954 views | HTML 3079 views | ?

Abstract

Zhen Wang1,5,*, Xiaoshan Xu1,*, Nan Liu1,*, Yingduan Cheng1,2, Weilin Jin3, Pengxing Zhang1, Xin Wang4, Hongwei Yang4, Hui Liu1 and Yanyang Tu1,4,*

1Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical, University, Xi’an 710038, China

2Department of Research, Cipher Ground, North Brunswick, NJ 08902, USA

3Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

4Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

5Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi’an Jiao Tong University, Xi’an 710049, China

*These authors contributed equally to this work

Correspondence to:

Yanyang Tu, email: [email protected]

Keywords: glioblastoma multiforme; SOX9; PDK1; self-renewal; temozolomide

Received: June 05, 2017 Accepted: November 15, 2017 Published: November 30, 2017

ABSTRACT

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with limited therapeutic options. Glioma stem cell (GSC) is thought to be greatly responsible for glioma tumor progression and drug resistance. But the molecular mechanisms of GSC deriving recurrence and drug resistance are still unclear. SOX9 (sex-determining region Y (SRY)-box9 protein), a transcription factor expressed in most solid tumors, is reported as a key regulator involved in maintaining cancer hallmarks including the GSCs state. Previously, we have observed that silencing of SOX9 suppressed glioma cells proliferation both in vitro and in vivo. Here, we found that SOX9 was essential for GSC self-renewal. Silencing of SOX9 down-regulated a broad range of stem cell markers and inhibited glioma cell colony and sphere formation. We identified pyruvate dehydrogenase kinase 1 (PDK1) as a target gene of SOX9 using microarray analyses. PDK1 inactivation greatly inhibited glioma cell colony and sphere formation and sensitized glioma spheres to temozolomide (TMZ) toxicity. In addition, SOX9-shRNA and PDK1 inhibitor could greatly sensitize GSC to TMZ in vivo. Taken together, our data reveals that SOX9-PDK1 axis is a key regulator of GSC self-renewal and GSC temozolomide resistance. These findings may provide help for future human GBM therapy.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 22773

Publication Alerts

Research Papers:

SOX9-PDK1 axis is essential for glioma stem cell self-renewal and temozolomide resistance

Abstract