TY  - JOUR
AU  - Barbosa, Silvia
AU  - Laureano, Natalia Koerich
AU  - Hadiwikarta, Wahyu Wijaya
AU  - Visioli, Fernanda
AU  - Bonrouhi, Mahnaz
AU  - Pajdzik, Kinga
AU  - Conde-Lopez, Cristina
AU  - Herold-Mende, Christel
AU  - Eidt, Gustavo
AU  - Langie, Renan
AU  - Lamers, Marcelo Lazzaron
AU  - Stögbauer, Fabian
AU  - Hess, Jochen
AU  - Kurth, Ina
AU  - Jou, Adriana
TI  - The Role of SOX2 and SOX9 in Radioresistance and Tumor Recurrence.
JO  - Cancers
VL  - 16
IS  - 2
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2024-00222
SP  - 439
PY  - 2024
N1  - #EA:E220#LA:E220#LA:E221#
AB  - Head and neck squamous cell carcinoma (HNSCC) exhibits considerable variability in patient outcome. It has been reported that SOX2 plays a role in proliferation, tumor growth, drug resistance, and metastasis in a variety of cancer types. Additionally, SOX9 has been implicated in immune tolerance and treatment failures. SOX2 and SOX9 induce treatment failure by a molecular mechanism that has not yet been elucidated. This study explores the inverse association of SOX2/SOX9 and their distinct expression in tumors, influencing the tumor microenvironment and radiotherapy responses. Through public RNA sequencing data, human biopsy samples, and knockdown cellular models, we explored the effects of inverted SOX2 and SOX9 expression. We found that patients expressing SOX2LowSOX9High showed decreased survival compared to SOX2HighSOX9Low. A survival analysis of patients stratified by radiotherapy and human papillomavirus brings additional clinical relevance. We identified a gene set signature comprising newly discovered candidate genes resulting from inverted SOX2/SOX9 expression. Moreover, the TGF-β pathway emerges as a significant predicted contributor to the overexpression of these candidate genes. In vitro findings reveal that silencing SOX2 enhances tumor radioresistance, while SOX9 silencing enhances radiosensitivity. These discoveries lay the groundwork for further studies on the therapeutic potential of transcription factors in optimizing HNSCC treatment.
KW  - HNSCC (Other)
KW  - HPV negative (Other)
KW  - SOX2 (Other)
KW  - SOX9 (Other)
KW  - gene set signature (Other)
KW  - metastasis (Other)
KW  - radiation treatment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38275880
C2  - pmc:PMC10814462
DO  - DOI:10.3390/cancers16020439
UR  - https://inrepo02.dkfz.de/record/287407
ER  -