Stoeckl, Sabine and Lindner, Georg and Li, Shushan and Schuster, Philipp and Haferkamp, Sebastian and Wagner, Ferdinand and Prodinger, Peter M. and Multhoff, Gabriele and Boxberg, Melanie and Hillmann, Axel and Bauer, Richard J. and Graessel, Susanne (2020) SOX9 Knockout Induces Polyploidy and Changes Sensitivity to Tumor Treatment Strategies in a Chondrosarcoma Cell Line. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (20): 7627. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
As most chemotherapeutic drugs are ineffective in the treatment of chondrosarcoma, we studied the expression pattern and function of SOX9, the master transcription factor for chondrogenesis, in chondrosarcoma, to understand the basic molecular principles needed for engineering new targeted therapies. Our study shows an increase in SOX9 expression in chondrosarcoma compared to normal cartilage, but a decrease when the tumors are finally defined as dedifferentiated chondrosarcoma (DDCS). In DDCS, SOX9 is almost completely absent in the non-chondroid, dedifferentiated compartments. CRISPR/Cas9-mediated knockout of SOX9 in a human chondrosarcoma cell line (HTB94) results in reduced proliferation, clonogenicity and migration, accompanied by an inability to activate MMP13. In contrast, adhesion, apoptosis and polyploidy formation are favored after SOX9 deletion, probably involving BCL2 and survivin. The siRNA-mediated SOX9 knockdown partially confirmed these results, suggesting the need for a certain SOX9 threshold for particular cancer-related events. To increase the efficacy of chondrosarcoma therapies, potential therapeutic approaches were analyzed in SOX9 knockout cells. Here, we found an increased impact of doxorubicin, but a reduced sensitivity for oncolytic virus treatment. Our observations present novel insight into the role of SOX9 in chondrosarcoma biology and could thereby help to overcome the obstacle of drug resistance and limited therapy options.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEDIFFERENTIATED CHONDROSARCOMA; MOLECULAR-MECHANISMS; PROGNOSTIC-FACTORS; CERVICAL-CANCER; DNA-PLOIDY; EXPRESSION; P53; HETEROZYGOSITY; PROGRESSION; ANEUPLOIDY; SOX9; transcription factor; chondrosarcoma; polyploidy; MMP13; CRISPR; Cas9 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2021 09:44 |
| Last Modified: | 09 Mar 2021 09:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43633 |
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